| http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15506563
Eur
J Cell Biol. 2004 Aug;83(8):389-402.
Fluoride
causes reversible dispersal of Golgi cisternae and matrix
in neuroendocrine cells.
Back
N, Litonius E, Mains RE, Eipper BA.
Department
of Anatomy, Institute of Biomedicine, Biomedicum Helsinki,
University of Helsinki, Finland. nils.back@helsinki.fi
A
role for heterotrimeric G proteins in the regulation of
Golgi function and formation of secretory granules is
generally accepted. We set out to study the effect of
activation of heterotrimeric G proteins by aluminum
fluoride on secretory granule formation in AtT-20
corticotropic tumor cells and in melanotrophs from the
rat pituitary. In AtT-20 cells,
treatment with aluminum fluoride or fluoride alone for
60 min induced complete dispersal of Golgi, ER-Golgi intermediate
compartment and Golgi matrix markers,
while betaCOP immunoreactiviy retained a juxtanuclear
position and TGN38 was unaffected.
Electron microscopy showed compression of Golgi
cisternae followed by conversion of the Golgi stacks into
clusters of tubular and vesicular elements. In the melanotroph
of the rat pituitary a similar compression of Golgi cisternae
was observed, followed by a progressive loss of cisternae
from the stacks. As shown in other cells, brefeldin A
induced redistribution of the Golgi matrix protein GM130
to punctate structures in the cytoplasm in AtT-20 cells,
while mannosidase II immunoreactivity was completely dispersed.
Fluoride induced a complete dispersal of mannosidase II
and GM130 immunoreactivity. The effect of fluoride
was fully reversible with reestablishment of normal mannosidase
II and GM130 immunoreactivity within 2 h. After 1 h of
recovery, showing varying stages of reassembly, the patterns
of mannosidase II and GM130 immunoreactivity were identical
in individual cells, indicating that Golgi matrix and
cisternae reassemble with similar kinetics during recovery
from fluoride treatment. Instead
of a specific aluminum fluoride effect on secretory granule
formation in the trans-Golgi network, we thus observe
a unique form of Golgi dispersal induced by fluoride alone,
possibly via its action as a phosphatase inhibitor.
PMID:
15506563 [PubMed - in process]
|
Online
14 September 2004. EHP (Environmental
Health Perspectives).
A
Quantitative Look at Fluorosis and Fluoride Exposure and
Intake of Children Using a Health Risk Assessment Approach.
Serap
Erdal (1) and Susan N. Buchanan (2).
(1)
Division of Environmental and Occupational Health Sciences,
School of Public Health, University of Illinois at Chicago,
Chicago, Illinois.
(2) Department of Occupational Medicine and Department
of Family Medicine, College of Medicine,
University of Illinois at Chicago, Chicago, Illinois.
The
prevalence of dental flourosis in the United States has
increased during the last thirty years. In this study,
a mathematical model commonly employed by the USEPA is
used to estimate average daily intake of fluoride via
all applicable exposure pathways contributing to fluorosis
risk for infants and children living in hypothetical fluoridated
and non-fluoridated communities. Hazard Quotient for each
exposure pathway and Hazard Indices are also estimated
for exposure conditions representative of central tendency
(CTE) and reasonable maximum exposure conditions (RME).
The exposure pathways considered are uptake of fluoride
via fluoridated drinking water, beverages, cow’s
milk, foods, and fluoride supplements for both age groups.
Additionally, consumption of infant formula for infants
and inadvertent swallowing of toothpaste while brushing
and soil for children are also considered. The cumulative
daily fluoride intake in fluoridated areas was estimated
as 0.20 and 0.11 mg/kg-d for RME and CTE scenarios, respectively,
for infants. On the other hand, the RME and CTE estimates
for children were 0.23 and 0.06 mg/kg-d, respectively.
In areas where municipal water is not fluoridated, our
RME and CTE estimates for cumulative daily average intake
were 0.11 and 0.08 mg/kg-d for infants and 0.21 and 0.06
mg/kg-d for children, respectively. Our theoretical estimates
are in good agreement with measurement-based estimates
reported in the literature. Although CTE estimates were
within the optimum range for caries prevention the RME
estimates were above the upper tolerable intake limit.
This suggests that a segment of the children population
may likely be at risk for fluorosis.
|
J
Natl Cancer Inst. 2004 May
19;96(10):802-3.
Extended
follow-up of cancer incidence in fluoride-exposed workers.
Grandjean P, Olsen JH.
Publication Types:
* Letter
Excerpt:
“We previously reported the cancer morbidity from
1943 through 1987 for 422 male cryolite workers employed
for more than 6 months at the mill from 1924 through 1961.
We observed excess incidences of primary cancer of the
lungs and of urinary bladder tumors (including bladder
papilloma)... We have now extended the follow-up of this
cohort by 12 years, at the end of which the total percentage
of cohort members who had died exceeded 90%. These
findings amplify our previous observation of increased
bladder cancer rates among cryolite workers... We therefore
believe that fluoride should be considered a possible
cause of bladder cancer and a contributory cause of primary
lung cancer.”
Note:
See FAN
Science Watch #11 for a discussion of these findings.
|
Toxicology
2004 Volume
200, Issues 2-3, 5 August, Pages 169-177
Decreased
nicotinic receptors in PC12 cells and rat brains influenced
by fluoride toxicity—a mechanism relating to a damage
at the level in post-transcription of the receptor genes
Ke-Ren
Shana (a), Xiao-Lan Qia (a), Yi-Guo Longb (b), Agneta
Nordbergc (c) and Zhi-Zhong Guan (a,b,c)
(a)
Department of Molecular Biology, Guiyang Medical College,
Guiyang 550004, Guizhou, PR China
(b)
Department of Pathology, Guiyang Medical College, Guiyang
550004, Guizhou, PR China
(c)
Department of Neurotec, Division of Molecular Neuropharmacology,
Karolinska Institutet, SE-141 86, Stockholm, Sweden
In order to reveal mechanisms of the decreased nicotinic
acetylcholine receptors (nAChRs) resulted from fluoride
toxicity, we treated PC12 cells by different concentrations
of fluoride (0.1–100 ppm) for 48 h, and
exposed rats to high doses of fluoride (30 and 100 ppm)
in their drinking water for 7 months. The expression of
nAChRs at mRNA and protein levels, neurotoxicity and oxidative
stress were analyzed in the study. The results indicated
that there were no significant changes at mRNA level of
the nAChR 3, 7, 2 subunits in PC12 cells, and 4, 7, 2
subunits in rat brains between the groups with fluorosis
and controls. A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) reduction, and increased
levels of protein oxidation and lipid peroxidation were
observe in PC12 cells treated with high doses of
fluoride or rat brains with chronic fluorosis. The decreases
of nAChR 3 and 7 subunit proteins in PC12 cells resulted
from fluoride toxicity were mostly prevented by a pretreatment
with antioxidant. The results suggest
that the deficit of nAChRs induced by fluoride toxicity
occurs at the level of post-transcription of the receptor
gene, in which a mechanism might be involved in the damage
by oxidative stress.
|
Journal
of Allergy and Clinical Immunology
Volume 113, Issue 2, Supplement 1 , February 2004,
Page S66
Program
and Abstracts of papers presented during Scientific Sessions
- AAAAI 60th Annual Meeting
Effects
of fluoride and mercury on human cytokine response in
vitro
G. de Vos (a), E. Jerschowb, Z.
Liao (b) and D. Rosenstreich (b)
(a)
Department of Allergy and Immunology, Albert Einstein
College of Medicine, Bronx, NY, USA
(b) Allergy and Immunology, Albert Einstein College of
Medicine, Bronx, NY, USA
Rationale: Over the past 50 years individuals in westernized
societies have been increasingly exposed to mercury (e.g.
through contaminated fish and dental amalgam) and fluoride
(e.g. through drinking water, toothpaste and gels). Given
the increasing incidence of allergic diseases and the
known immunomodulatory effects of these agents, we investigated
their potential allergy-promoting activity.
Methods:
Peripheral blood mononuclear cells (PBMC) from 4 individuals
were cultured up to seven days in culture medium or in
culture media containing Con A in the presence or absence
of mercuric chloride (HgCl) or sodium fluoride (NaF).
Supernatants were harvested on days 2, 4 and 6 and IL-4
and gamma-IFN concentrations were measured by ELISA.
Results:
HgCl and NaF significantly suppressed Con A-induced gamma-IFN
production. Maximum suppression of gamma-IFN production
by HgCl occurred on day 6 (10.4% +/- 9.4% of the Con A
response) and by NaF on day 4 (8.3% +/- 7.2%). In contrast,
HgCl and NaF significantly increased Con A -induced IL-4
production, with a maximum on day 4 (362.9% +/- 365%)
and day 2 (660.8% +/- 894.72%), respectively. Neither
NaF nor HgCl significantly altered cytokine production
in unstimulated lymphocytes.
Conclusions:
HgCl and NaF seem to selectively
suppress Th1 activity and stimulate Th2 cytokine production
in vitro. Although preliminary, these findings suggest
that human exposure to mercury or fluoride maybe playing
a role in the observed increased incidence of allergic
diseases in the industrialized world.
|
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15196683
Neurosci
Lett. 2004 Jul 1;364(2):86-9.
"Low"
concentrations of sodium fluoride inhibit neurotransmitter
release from the guinea-pig superior cervical ganglion.
Borasio PG, Cervellati F, Pavan
B, Pareschi MC.
Department of Biology, Section of General Physiology,
University of Ferrara, Via L. Borsari 46, 44100 Ferrara,
Italy.
The role of G proteins and related second messenger system
on the modulation of acetylcholine release from [ [Formula:
see text] ]choline-preloaded guinea-pig superior cervical
ganglion was investigated using the potent general activator
NaF. The electrically evoked (1Hz, 5min) [ [Formula: see
text] ] release was inhibited by "low" F(-)
concentrations (1-2.5mM), by the adenylyl cyclase blocker
MDL 12330A (10microM), alone and in combination with 1mM
NaF, and increased by 0.5mM 8Br-cAMP, 100microM forskolin
and 0.5mM 3-isobutyl-1-methylxantine. No effect of 1mM
F(-) was observed on spontaneous release. Fluoride-induced
inhibition was counteracted by the G protein blocker sulmazole
(1mM), forskolin and alteration of calcium influx by increasing
[Ca(2+)](out) from 2.2 to 6mM, raising the rate of stimulation
(10Hz, 30s), or broadening the presynaptic action potential
with 10microM 4-aminopyridine and 50microM tetraethylammonium
chloride. Thus a NaF-sensitive G
protein, linked to cAMP synthesis, is determinant for
the inhibition of neurosecretion in this cholinergic synapse,
involving Ca(2+)-dependent mechanisms.
PMID: 15196683 [PubMed - in process]
|
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15621939
Biol
Trace Elem Res. 2004 Winter;102(1-3):199-208.
Effect
of chronic fluorosis on lipid peroxidation and histology
of kidney tissues in first- and second-generation rats.
Karaoz
E, Oncu M, Gulle K, Kanter M, Gultekin F, Karaoz S, Mumcu
E.
Kocaeli
University, Health High School, Kocaeli, Turkey.
This
experiment was designed to investigate the lipid peroxidation
and histological effects of chronic fluorosis on first-
and second-generation rat kidney tissues. Sixteen virgin
female Wistar rats were mated with eight males (2: 1)
for approx 12 h to obtain first-generation rats. Mating
was confirmed by the presence of sperm in vaginal smears.
Sperm in vaginal smears was observed in 10 of 16 rats
(d 0). These rats were identified as pregnant and included
in this experiment. Pregnant rats were divided into two
experimental groups (control and fluoride-supplemented),
each containing five rats. The pregnant rats in the fluoride-supplemented
group were exposed to 30 mg/L sodium fluoride (NaF) in
commercial drinking water containing 0.07 mg/L NaF throughout
the gestation and the lactation periods. After the lactation
period, young animals (first generation [F1]) were exposed
to the same amount of NaF in drinking water for 4 mo.
At the end of the 4-mo experimental period, nine randomly
chosen male rats (F1) were sacrificed, and the kidneys
were removed for the histological and lipid peroxidation
examinations. The remaining eight female rats were mated
with four males (2: 1) for approx 12 h to obtain second-generation
rats. Six female were identified as pregnant, and treated
similarly throughout the gestation and the lactation periods.
After the lactation period, the young male rats (second-generation
male rats [F2]) were also treated similarly for 4 mo.
At the end of the 4-mo experimental period, nine randomly
chosen male rats (F2) were sacrificed, and the kidneys
were removed for the histological and lipid peroxidation
examinations. The rats in the control groups underwent
the same procedure without NaF supplementation.
It was found that the plasma fluoride and kidney TBARS
levels of fluoride-supplemented F1 and F2 rats were higher
than controls. Hydropic epithelial cell degenerations
and moderate tubular dilatation were observed in some
proximal and distal tubules. There were markedly focal
mononuclear cell infiltrations and hemorrhage at some
areas of the interstitium, especially at the corticomedullar
junction. Mononuclear cell infiltrations were also evident
in some peritubular and perivascular areas. Most of the
vascular structures were congestive. Many Bowman capsules
were narrowed. The severe degenerative changes in most
of the shrunken glomerules and vascular congestion were
also observed.
PMID:
15621939 [PubMed - in process]
|
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15909416&query_hl=6
Ukr Biokhim Zh. 2004
Jan-Feb;76(1):39-47.
[Inactivation of Na+, K+ -ATPase from cattle
brain by sodium fluoride]
[Article in Ukrainian]
Kravtsova VV, Kravtsov OV.
The influence of the
physiological ligands and modifiers on the plasma membrane Na+,
K+ -ATPase from calf brain inactivation by sodium fluoride (NaF)
is studied. ATP-hydrolyzing activity of the enzyme was found to
be more stable as to NaF inhibition than its K+ -pNPPase activity.
The activatory ions of Na+, K+ -ATPase have different effects
on the process of the enzyme inhibition by NaF. K+ intensifies
inhibition, but Na+ does not affect it. An increase of [Mg2+free]
in the incubation medium (from 0.5 to 3.0 mM) rises the sensitivity
of Na+, K+ -ATPase to NaF inhibition. But an increase of [ATP]
from 0.3 to 1.5 mM has no effect on this process. Ca and Mg ions
modify Na+, K+ -ATPase inhibition by fluoride differently. Ca2+free
levels this process, and Mg2+free on the contrary increases it.
In the presence of Ca ions and in the neutral-alkaline medium
(pH 7.0-8.5) the recovery of activity of the transport ATPase
inhibited by-NaF takes place. Sodium citrate also protects both
ATP-hydrolizing and K-pNPPase activity of the Na+, K+ -ATPase
from NaF inhibition. Under the modifing membranous effects (the
treatment of plasma membranes by Ds-Na and digitonin) the partial
loss of Na+, K+ -ATPase sensitivity to NaF inhibition is observed.
It is concluded that Na+, K+ -ATPase inactivation by NaF depends
on the influence of the physiological ligands and modifiers as
well as on the integrity of membrane structure.
PMID: 15909416
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15597201
J Mol Model (Online).
2004 Dec;10(5-6):328-34. Epub 2004
Sep 17.
Quantitative structure-activity relationship
study on some benzodiazepine derivatives as anti-Alzheimer agents.
Debnath
B, Gayen S, Basu A, Srikanth K, Jha T.
Division of Medicinal
and Pharmaceutical Chemistry, Department of Pharmaceutical Technology,
Jadavpur
University, PO Box
No 17020, 700 032, Kolkata, India.
A QSAR study was performed
in an attempt to explore the pharmacophore of some benzodiazepine
derivatives as anti-Alzheimer agents for the inhibition of gamma-secretase.
The study, which used the electrotopological state atom (ETSA)
index, which encodes electronic and topological information, reveals
the importance of two phenyl rings-one substituted and another
unsubstituted, for the inhibition of the enzyme. Fluorine
substitution on the substituted phenyl ring has an important contribution
to the activity. R-configurations of the aliphatic chain
substituents provide the exact conformation of the molecules to
enter into the binding pockets of the receptor(s).FIGURE General
structure of benzodiazepine containing gamma-secretase inhibitors.
PMID: 15597201
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15549646
Calcif Tissue Int.
2004 Oct;75(4):313-320. Epub 2004
Jul 13.
Simultaneous Exposure of Excess Fluoride and Calcium Deficiency
Alters VDR, CaR, and Calbindin D 9 k mRNA Levels in Rat Duodenal
Mucosa.
Tiwari
S, Gupta SK, Kumar K, Trivedi R, Godbole MM.
Department of Endocrinology,
Sanjay Gandhi Postgraduate Institute of Medical Sciences, 226014,
Lucknow, India.
Fluoride ingestion
reduces intestinal calcium absorption; its molecular basis has
not been studied. We studied the mRNA expression of calcium-sensing
receptor (CaR), vitamin D receptor (VDR) and calbindin D 9 k (D
9 k) by northern blot analysis in the duodenal mucosa of rats.
Weanling pups fed with chow diet containing adequate calcium (0.5%
w/w) and drinking water (NaF < 1 ppm) served as controls (Group
I) and were studied at 9 and 15 weeks. The pups, born to rats
fed with a calcium-deficient diet (0.03%) and excess fluoride
water (NaF 50 ppm), were continued on the same diet and water
(Group II) until 9 weeks of age. Subsequently, Group II rats were
divided into 4 subgroups; 3 subgroups with fluoride free water
[II-A adequate calcium, II-B excess calcium (Ca 2%) and II-D calcium
deficient], whereas II-C received fluorinated water and adequate
calcium diet until 15 weeks. At 9 weeks, as compared to group-I,
group-II had decreased VDR ( P < 0.001) and D 9 k mRNA ( P
< 0.001), whereas CaR mRNA levels increased ( P < 0.05).
At 15 weeks, as compared to group-I, VDR mRNA further reduced
in group II-D ( P < 0.001) and II-C ( P < 0.001), whereas
it increased in group II-A. Removal of fluoride ingestion and
calcium replenishment increased D 9 k mRNA expression, maximally
in adequate calcium group ( P < 0.001), while it was further
reduced in group II-C ( P < 0.001). CaR expression decreased
significantly in all the groups. We conclude
that excess fluoride reduces the mRNA levels of VDR and D 9 k
in the duodenal mucosa of rats, thereby possibly reducing calcium
absorption. Calcium supplementation with simultaneous fluoride
removal improves their expression.
PMID: 15549646
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15386084
Bull Environ Contam
Toxicol. 2004 Jul;73(1):139-45.
No
abstract available
Interactions
of arsenic with fluorine, selenium, barium, and strontium in human
hepatic cells.
Saito
S, Yamauchi H, Yoshida K.
Department of Preventive
Medicine, St. Marianna University School of Medicine, Kawasaki
216-8511, Japan.
PMID: 15386084
[PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15638415
Rocz Akad Med Bialymst.
2004;49 Suppl 1:180-1.
Ultrastructural study of the mitochondria
in the submandibular gland, the pancreas and the liver of young
rats, exposed to NaF in drinking water.
Dabrowska
E, Balunowska M, Letko R, Szynaka B.
Department of Social
and Preventive Dentistry, Medical University of Bialystok, Poland.
helpdentamb@o2.pl
The aim of the experiment
was to determine the effect of fluoride on ultrastructural changes
in the submandibular gland, the pancreas and the liver. The experimental
rats received fluoride in aqueous solutions of sodium fluoride
at concentrations of 10.6 NaF/dm3 and 32.0 NaF/dm3. In
the ultrastructural examination, mitochondria were most damaged.
PMID: 15638415
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15504151
Basic Clin Pharmacol
Toxicol. 2004 Oct;95(4):162-5.
The effect
of tamoxifen and fluoride on bone mineral density, biomechanical
properties and blood lipids in ovariectomized rats.
Czerny
B, Pawlik A, Juzyszyn Z, Mysliwiec Z.
Department of Pharmacokinetics
and Therapeutic Drug Monitoring, Pomeranian Medical University,
Powstancow Wielkopolskich 72, PL-70-111 Szczecin, Poland.
The most important
aspect of therapy with fluoride and tamoxifen concerns its influence
on bone tissue and lipid metabolism. The aim of the study was
to evaluate the effect of tamoxifen and natrium
fluoride (NaF) on bone metabolism, biochemical properties
and blood lipids levels in ovariectomized rats. The study was
performed in Wistar rats divided into 5 subgroups: ovariectomized
controls, rats treated with NaF 20 mg/kg/24
hr, rats treated with NaF 20 mg/kg/24 hr+tamoxifen 2 mg/kg/24
hr, rats treated with NaF 20 mg/kg/24 hr plus tamoxifen 4 mg/kg/24
hr, and sham-operated controls. In ovariectomized rats
the increase of total cholesterol, low-density lipoproteins cholesterol
(LDL-cholesterol) as well as the decrease of bone mineral content,
bone mineral density and biomechanical properties was observed.
The therapy with NaF increased the level
of total cholesterol, LDL-cholesterol, triglycerides, bone mineral
density, bone mineral content. In this group the decrease
of bone strength and stiffness was observed. The administration
of tamoxifen reduced the changes in plasma lipid levels, but did
not improve the biomechanical properties of bone tissue.
PMID: 15504151
[PubMed - in process]
Fluoride (2004)
Vol. 37; No 1; 7-12.
Fluoride effects
on glutathione peroxidase and lipid peroxidation in rats
I Inkielewicz
(a), J Krechniak (a,b),
(a) Department of Toxicology,
Medical University of Gdansk, Poland.
(b) For correspondence: Dept. of Toxicology, Medical University
of Gdansk, 80-416, Al. Gen. Hallera 107, Poland. Email: woczar@amg.gda.pl
SUMMARY: Eight-week
old male Wistar rats weighing 180 g were given sodium
fluoride in drinking water at a concentration of 5 and
25 mg F/L for 12 weeks. Control animals received tap water containing
0.3 mg F/L. The activity of glutathione peroxidase and the concentration
of malondialdehye (MDA) were determined in kidney, liver, brain,
testis, and blood or plasma. In exposed animals the activity of
glutathione peroxidase decreased significantly, and the concentration
of MDA increased in a dose and exposure-time dependent manner.
The results of this study confirm other
reports that fluoride induces free radical toxicity in animals.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15388248
Toxicology. 2004
Nov 15;204(2-3):219-28.
Effect of fluoride intoxication on lipidperoxidation
and antioxidant status in experimental rats.
Shanthakumari
D, Srinivasalu S, Subramanian S.
Department of Biochemistry
and Molecular Biology, University of Madras, Guindy Campus, Chennai
600025, Tamil Nadu, India.
Fluoride is a potent
enzyme poison. Thirty ground water samples from Vellore District,
Tamil Nadu, India were analysed for fluoride content and it was
revealed that the fluoride content of 24 samples were over and
above the permissible limits. In the present
study, the experimental rats were orally treated with 25ppm of
fluoride/rat/day for 8 and 16 weeks, respectively, and
the levels of lipid peroxidation and antioxidant enzymes were
studied to evaluate fluoride intoxication. An
increase in the level of lipid peroxides along with a concomitant
decrease in the activities of superoxide dismutase (SOD), catalase
(CAT), glutathione peroxidase (GPx) and reduced glutathione content
were observed in fluoride administered groups of rats. The altered
antioxidant status may be attributed to the increased generation
of free radicals.
PMID: 15388248
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15386948
Biomed Environ Sci.
2004 Jun;17(2):217-22.
Effects of
fluoride on lipid peroxidation, DNA damage and apoptosis in human
embryo hepatocytes.
Wang
AG, Xia T, Chu QL, Zhang M, Liu F, Chen XM, Yang KD.
Department of Environmental
Health, Tongji Medical College, Huazhong University of Science
and Technology, Wuhan 430030, Hubei, China. wangaiguo@mails.tjmu.edu.cn
OBJECTIVE: To investigate
the effects of fluoride on lipid peroxidation, DNA damage and
apoptosis in human embryo hepatocyte L-02 cells.
METHODS: Lipid peroxide (LPO) level, reduced glutathione (GSH)
content, DNA damage, apoptosis, and cell cycle analysis were measured
after in vitro cultured L-02 cells were exposed to sodium fluoride
at different doses (40 microg/mL, 80 microg/mL, and 160 microg/mL)
for 24 hours.
RESULTS: Fluoride caused an increase of LPO levels and a decrease
of GSH content in L-02 cells. There appeared to be an obvious
dose-effect relationship between the fluoride concentration and
the observed changes. Fluoride also caused DNA damage and apoptosis
and increased the cell number in S phase of cell cycle in the
cells tested. There was a statistically significant difference
in DNA damage and apoptosis when comparing the high dose of fluoride
treated cells with the low dose of fluoride treated cells.
CONCLUSION: Fluoride
can cause lipid peroxidation, DNA damage, and apoptosis in the
L-02 cell experimental model and there is a significant positive
correlation between fluoride concentration and these pathological
changes.
PMID: 15386948
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15449681
Arkh Patol. 2004
Jul-Aug;66(4):13-6.
[Human epiphyseal
concrements in schizophrenia]
[Article in Russian]
[No authors listed]
The epiphysis is a
gland containing firm extracellular bodies (brain sand) the number
of which increases with age. Microscopy and roentgen microtomography
showed that in some cases of schizophrenia the amount of brain
sand decreases. In parallel, cytoplasm of
pinealocytes appears to contain concrements of a new type--irregular
hollow spheres of 0.1-1.5 microm in size. They may contain fluoride.
Typical hydroxyapatite retaining organic stroma may dissolve starting
from the center both in health and schizophrenia.
PMID: 15449681
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15461257
Wei Sheng Yan Jiu.
2004 Jul;33(4):400-2.
[Effects on
DNA damage and apoptosis and p53 protein expression induced by
fluoride in human embryo hepatocytes]
[Article in Chinese]
Ha
J, Chu Q, Wang A, Xia T, Yang K.
Hubei Vocational-Technical
College, Xiaogan 432000, China.
OBJECTIVE: To study
the effects of DNA damage and apoptosis and p53 expression, and
to explore the relationship between apoptosis and p53 expression
in human embryo hepatocytes induced by fluoride.
METHODS: The rate of DNA damage, apoptosis and the level of p53
expression were investigated after the cells were incubated with
sodium fluoride for about 24 hours. The concentrations of sodium
fluoride of the control, A, B and C group were 0 microg/ml, 40
microg/ ml, 80 microg/ml and 160 microg/ml individually.
RESULTS: The
rate of DNA damage of every group treated with sodium fluoride
were significantly higher than the control group (P < 0.05).
The percentage of apoptosis of B and C groups increased apparently
(P < 0.05). The level of p53 expression of B and C groups were
significantly higher than the control group (P < 0.01).
CONCLUSION: Fluoride
can increase the rate of DNA damage, and induce apoptosis and
expression of p53 in human embryo hepatocytes. Furthermore, both
apoptosis and the level of p53 expression, there exists a rise
tendency with the increase concentration of fluoride.
PMID: 15461257
[PubMed - in process]
Fish & Shellfish Immunology
2004 - Article in Press, Available
online September 11, 2004
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15475311
Fish & Shellfish
Immunology 2005 Feb;18(2):149-162.
Signal transduction
of the prophenoloxidase activating system of prawn haemocytes
triggered by CpG oligodeoxynucleotides
Che-Pei
Chuo (a), Shu-Mei Liang (b) and Hung-Hung Sung (a)
(a) Department of Microbiology, Soochow University, Taipei, Taiwan,
ROC
(b) Institute of Bioagricultural Sciences, Academia Sinica, Taipei,
Taiwan, ROC
Intracellular phenoloxidase (PO) activity in haemocyte lysate
supernatant (HLS) of giant freshwater prawn (Macrobrachium rosenbergii)
was shown to be enhanced by CpG oligodeoxynucleotide (ODN) 2006,
but not by so-ODN13. When haemocytes were treated in vitro with
50 mg/ml of ODN2006 for 30 min, the increases in both
intra- and extracellular stimulated PO activity (POS) and extracellular
total PO activity (POT) and the reduction of POT suggest that
the PO activity of haemocytes is enhanced by ODN2006 stimulation,
but new prophenoloxidase (proPO) is not synthesised. In an attempt
to determine which signal transduction pathway is involved in
the activation of the proPO system, haemocytes were separately
treated with activators or inhibitors of specific signalling components.
The results show that there was an increase
in both intra- and extracellular POT of haemocytes treated with
sodium fluoride (a G-protein activator); the addition of
phosphokinase A (PKA)-activating 8-bromo-cAMP to haemocytes only
increased intracellular POT, and the addition of either phorbol-12-myristate-13-acetate
(PMA; a phosphokinase C (PKC) activator) or caffeine (a phosphodiesterase
inhibitor) only increased extracellular POT. When PMA-stimulated
haemocytes were treated with chelerythrine (a PKC inhibitor),
the induced extracellular POT was significantly reduced. Furthermore,
the study of ODN2006-stimulated haemocytes treated with chelerythrine
or palmitoyl-DL-carnitine (a PKC inhibitor) showed that the enhancement
effects of ODN2006 on the intra- and extracellular POS and extracellular
POT were significantly decreased. ODN-stimulated haemocytes treated
with genistein (an inhibitor of protein tyrosine kinase) showed
a further increase in extracellular POT, but the other PO activities
remained the same as those of the ODN-stimulated group. These
results suggest that the activation of the proPO system of prawn
haemocytes, including degranulation and PO activity, is induced
by ODN2006 via a PKC-activating signalling pathway, but negatively
regulated via the tyrosine kinase pathway.
Inhibitors and activators: 8-Bromo-cAMP:
a PKA activator; Caffeine: a phosphodiesterase inhibitor; Chelerythrine:
a PKC inhibitor; Genistein: an inhibitor of protein tyrosine kinase;
Palmitoyl-DL-carnitine: a PKC inhibitor; PMA: a PKC activator;
Sodium fluoride (NaF): a G-protein activator
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15477420
Circulation. 2004
Oct 19;110(16):2326-32. Epub 2004 Oct 11.
Prostaglandin
E2--mediated relaxation of the ductus arteriosus: effects of gestational
age on g protein-coupled receptor expression, signaling, and vasomotor
control.
Waleh
N, Kajino H, Marrache AM, Ginzinger D, Roman C, Seidner SR, Moss
TJ, Fouron JC, Vazquez-Tello A, Chemtob S, Clyman RI.
Cardiovascular Research
Institute and Department of Pediatrics, University of California,
San Francisco, San Francisco, Calif 94143-0544, USA.
BACKGROUND: In the
preterm newborn, a patent ductus arteriosus is in large part a
result of the increased sensitivity of the immature ductus to
prostaglandin E2 (PGE2). PGE2 acts through 3 G protein-coupled
receptors (EP2, EP3, and EP4) that activate both adenyl cyclase
and K(ATP) channels. We explored these pathways to identify the
mechanisms responsible for the increased sensitivity of the immature
ductus to PGE2.
METHODS AND RESULTS: We measured EP receptor content (mRNA and
protein), receptor binding, cAMP production, and isometric tension
in rings of ductus taken from immature (65% gestation) and mature
(95% gestation) sheep and baboon fetuses. Ductus relaxation and
cAMP generation were augmented in response to selective EP receptor
agonists in the immature ductus. 8-Br-cAMP, a stable cAMP analogue,
produced greater relaxation in the immature ductus. In the presence
of a selective protein kinase A inhibitor, Rp-8-CPT cAMPS, the
developmental differences in sensitivity to PGE2 could no longer
be demonstrated. EP2, EP3, and EP4 receptor densities were higher
in immature ductus, despite similar receptor mRNA and protein
contents at the 2 gestational ages. In contrast,
forskolin and NaF, direct activators of adenyl cyclase and Gs,
respectively, elicited comparable increases in cAMP in both age
groups. KATP channel inhibition also had similar effects
on PGE2-induced relaxation in both age groups.
CONCLUSIONS: Two mechanisms explain the increased sensitivity
of the immature ductus to PGE2: (1) increased cAMP production
because of increased binding of PGE2 to the individual EP receptors
and (2) increased potency of cAMP on protein kinase A-regulated
pathways.
PMID: 15477420
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15501038
Bioorg Med Chem Lett.
2004 Dec 6;14(23):5769-5773.
Carbonic anhydrase inhibitors: inhibition of the membrane-bound
human isozyme IV with anions.
Innocenti
A, Firnges MA, Antel J, Wurl M, Scozzafava A, Supuran CT.
Universita degli Studi
di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via
della Lastruccia 3, I-50019 Sesto Fiorentino (Firenze), Italy.
The membrane-associated
human isozyme of carbonic anhydrase, hCA IV, has been investigated
for its interaction with anion inhibitors, for the CO(2) hydration
reaction catalyzed by this enzyme. Surprisingly, halides were
observed to act as potent hCA IV inhibitors, with inhibition constants
in the range of 70-90Î1⁄4M, although most of these
ions, and especially fluoride, the best
hCA IV inhibitor among the halides, are weak inhibitors
of other isozymes, such as hCA I, II and V. The metal poisons
cyanate, cyanide and hydrogen sulfide were weaker hCA IV inhibitors
(K(i)'s in the range of 0.6-3.9mM), whereas thiocyanate, azide,
nitrate and nitrite showed even weaker inhibitory properties (K(i)'s
in the range of 30.8-65.1mM). Sulfate was a good hCA IV inhibitor
(K(i) of 9mM), although it is a much weaker inhibitor of isozymes
I, II, V and IX. Excellent hCA IV inhibitory properties showed
sulfamic acid, sulfamide, phenylboronic acid and phenylarsonic
acid, with K(i)'s in the range of 0.87-0.93Î1⁄4M,
whereas their affinities for the other investigated isozymes were
in the millimolar range. The interaction of some anions with the
mitochondrial isozyme hCA V has also been investigated for the
first time here. It has been observed that among all these isozymes,
hCA V has the lowest affinity for bicarbonate and carbonate (K(i)'s
in the range of 82-95mM), which may represent an evolutionary
adaptation of this isozyme to the rather alkaline environment
(pH8.5) within the mitochondria, where hCA V plays important functions
in some biosynthetic reactions involving carboxylating enzymes
(pyruvate carboxylase and acetyl coenzyme A carboxylase). There
are important differences of affinity for anions between the two
membrane-associated isozymes, hCA IV and hCA IX.
PMID: 15501038
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15308711
J Virol. 2004
Sep;78(17):9154-63.
Subcellular localization and calcium and pH requirements
for proteolytic processing of the Hendra virus fusion protein.
Pager
CT, Wurth MA, Dutch RE.
Department of Molecular
and Cellular Biochemistry, University of Kentucky, Lexington,
Kentucky 40536-0298, USA.
Proteolytic cleavage
of the Hendra virus fusion (F) protein results in the formation
of disulfide-linked F1 and F2 subunits, with cleavage occurring
after residue K109 in the sequence GDVK/L. This unusual cleavage
site and efficient propagation of Hendra virus in a furin-deficient
cell line indicate that the Hendra F protein is not cleaved by
furin, the protease responsible for proteolytic activation of
many viral fusion proteins. To identify the subcellular site of
Hendra F processing, Vero cells transfected with pCAGGS-Hendra
F or pCAGGS-SV5 F were metabolically labeled and chased in the
absence and presence of inhibitors of exocytosis. The
addition of carbonyl-cyanide-3-chlorophenylhydrazone, monensin,
brefeldin A, or NaF-AlCl3 or incubation of cells at 20 degrees
C all inhibited processing of the Hendra F protein, suggesting
that cleavage of Hendra F occurs either in secretory vesicles
budding from the trans-Golgi network or at the cell surface.
In contrast to proteolytic cleavage of the simian virus 5 (SV5)
F protein by the Ca(2+)-dependent protease furin, proteolytic
cleavage of the Hendra F protein was not significantly inhibited
by decreases in Ca2+ levels following incubation with EGTA or
A23187. However, in the presence of weak amines and H+ V-ATPase
inhibitors, known to raise intracellular pH, cleavage of Hendra
F protein was inhibited while processing of the SV5 F protein
was not significantly affected. The subcellular location, sensitivity
to pH changes, and decreased Ca2+ requirement suggest that the
protease responsible for cleavage of Hendra F protein differs
from proteases previously shown to be involved in the processing
of other viral glycoproteins.
PMID: 15308711
[PubMed - indexed for MEDLINE]
Full
free report available at http://www.fluoridealert.org/pesticides/f.turk.j.vet.anim.sc.2004.pdf
Turk J Vet Anim Sci
28 (2004) 591-595
The Effect
of Acute Fluoride Poisoning on Nitric Oxide and Methemoglobin
Formation in the Guinea pig
Meltem
Sireli (a), Aziz Bulbul (b)
(a) Department of Physiology,
Faculty of Veterinary Medicine, Ankara University, Ankara - TURKEY
(b) Department of Physiology, Faculty of Veterinary Medicine,
Afyon Kocatepe University, Afyon - TURKEY
To study the effect
of acute fluoride poisoning on nitric oxide and methemoglobin
formation, 250 mg/kg bw sodium fluoride was applied alone and
verapamil was applied together with fluoride. Blood nitric oxide
(Griess reaction) and calcium levels; hemoglobin, methemoglobin
and hematocrit values; and erythrocyte counts were determined
and compared with those of the controls. After the fluoride application
it was found that there was a relative relationship between the
increase in nitric oxide and methemoglobin levels and the decrease
in calcium, hemoglobin and hematocrit levels and erythrocyte count.
It was concluded that the increase seen in blood nitric oxide
levels as a result of the ionophore effect of fluoride could come
from cNOS, as that increase is related to the decrease in calcium
amount.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15306227
Cardiovasc Res. 2004
Sep 1;63(4):709-18.
Modulation of G-protein expression and adenylyl cyclase
signaling by high glucose in vascular smooth muscle.
Hashim
S, Li Y, Nagakura A, Takeo S, Anand-Srivastava MB.
Department of Physiology
and Groupe de recherche sur le systeme nerveux autonome (GRSNA),
Faculty of Medicine, Pavillon Paul G. Desmarais, University of
Montreal, C.P. 6128, Succ. Centre-ville, Montreal, Quebec, Canada
H3T 1J4.
Objective:
We have recently shown a decreased expression of Gialpha proteins
and associated functions in aorta from short term (5 days) streptozotocin-induced
diabetic rats. Since hyperglycemia is one of the underlying causes
of diabetes-induced cardiovascular complications, it was of interest
to examine if hyperglycemia may play a direct role in down regulating
the expression of Gialpha in vascular smooth muscle cells of diabetic
subjects. For this, the effect of high glucose treatment on Gialpha
protein expression and adenylyl cyclase signaling in intact aorta
and vascular smooth muscle cells (A10 cells) was investigated.
Methods: The cells were grown in normal glucose
(5.5 mM) medium and were subsequently exposed to high glucose
(26 mM) or normal medium for various time periods (24-96 h). Aorta
from control rats were exposed to normal and high glucose medium
for 72 h. The levels of G-proteins were determined by immunoblotting
using specific antibodies. Adenylyl cyclase activity stimulated
or inhibited by agonists was determined to examine the functions
of G-proteins.
Results: The levels of Gialpha-2 and Gialpha-3
proteins in membranes from A10 cells and aorta exposed to high
glucose for 3 or 4 days were significantly decreased as compared
to control cells and control aorta, respectively, whereas the
levels of Gsalpha protein were not altered. In addition, receptor-dependent
and -independent functions of Gialpha proteins were attenuated
in hyperglycemic cells, as demonstrated by inhibition of forskolin
(FSK)-stimulated adenylyl cyclase activity by low concentration
of GTPgammaS or by angiotensin II (Ang II), oxotremorine or C-ANP(4-23)
(a ring deleted analog of atrial natriuretic peptide).
On the other hand, the stimulatory effects of GTPgammaS, glucagon,
isoproterenol, FSK and sodium fluoride on adenylyl cyclase were
significantly augmented in hyperglycemic cells as compared to
control cells, whereas basal adenylyl cyclase activity
was significantly lower in hyperglycemic cells as compared to
control cells.
Conclusion: These results indicate that high
glucose decreased the levels and functions of Gi proteins in A10
VSMC and aorta. It may thus be suggested that decreased levels
and activity of Gi proteins and adenylyl cyclase signaling induced
by hyperglycemia may be one of the important mechanisms contributing
to the cardiovascular complications associated with diabetes.
PMID: 15306227
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15212813
Toxicology. 2004
Aug 5;200(2-3):169-77.
Decreased nicotinic receptors in PC12 cells and rat brains
influenced by fluoride toxicity-a mechanism relating to a damage
at the level in post-transcription of the receptor genes.
Ke-Ren
Shan (a), Xiao-Lan Qi (a), Yi-Guo Long (b), Agneta Nordberg (c)
and Zhi-Zhong Guan (a, b, c)
(a) Department of Molecular
Biology, Guiyang Medical College, Guiyang 550004, Guizhou, PR
China
(b) Department of Pathology, Guiyang Medical College, Guiyang
550004, Guizhou, PR China
(c) Department of Neurotec, Division of Molecular Neuropharmacology,
Karolinska Institutet, SE-141 86, Stockholm, Sweden
In order to reveal mechanisms of the decreased nicotinic acetylcholine
receptors (nAChRs) resulted from fluoride toxicity, we treated
PC12 cells by different concentrations of fluoride (0.1-100ppm)
for 48h, and exposed rats to high doses of fluoride (30 and 100ppm)
in their drinking water for 7 months. The expression of nAChRs
at mRNA and protein levels, neurotoxicity and oxidative stress
were analyzed in the study. The results indicated that there were
no significant changes at mRNA level of the nAChR alpha3, alpha7,
beta2 subunits in PC12 cells, and alpha4, alpha7, beta2 subunits
in rat brains between the groups with fluorosis and controls.
A significant decline in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) reduction, and increased levels of protein oxidation
and lipid peroxidation were observe in PC12 cells treated with
high doses of fluoride or rat brains with chronic fluorosis. The
decreases of nAChR alpha3 and alpha7 subunit proteins in PC12
cells resulted from fluoride toxicity were mostly prevented by
a pretreatment with antioxidant. The results
suggest that the deficit of nAChRs induced by fluoride toxicity
occurs at the level of post-transcription of the receptor gene,
in which a mechanism might be involved in the damage by oxidative
stress.
PMID: 15212813 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15208994
Wei Sheng Yan Jiu.
2004 Mar;33(2):158-61.
[Influence
of combined iodine and fluoride on phospholipid and fatty acid
composition in brain cells of rats]
[Article in Chinese]
Shen X, Zhang Z, Xu X.
College of Life and Enviroment Science, Zhejiang Normal University,
Jinhua 321004, China.
OBJECTIVE: Investigating the influence of combined iodine and
fluoride on phospholipid and fatty acid composition in brain cells
of rats.
METHODS: Five groups of rats were provided with deionized drinking
water containing 0 and 150 mg/L NaF, and containing both 150 mg/L
NaF and 0.003, 0.03 or 3 mg/L KI respectively for 5 months. Then
phospholipid and fatty acid composition were determined using
liquid chromatography.
RESULTS: The phospholipid composition had no obvious change. The
high concentration fluoride (150 mg/L) and high concentration
Iodine (3 mg/L) with high concentration fluoride could cause significant
changes of the fatty acid composition in brain cells of rats,
the proportion of unsaturated fatty acid (C18:2) was significantly
decreased and the saturated fatty acid (C12:0) increased obviously.
The antagonistic action of 0.03 mg/L KI drinking water on this
kind of influence induced by 150 mg/L NaF was the most evident,
whereas that of 3 mg/L KI was action of synergetic toxicity.
CONCLUSION: Fluorosis had obvious influence
on phospholipid and fatty acid composition in brain cells of rats,
and its mechanism might be associated with action of lipid peroxidation,
and 0.03 mg/L KI is the optimal concentration for the antagonistic
action with this influence from fluorosis.
PMID: 15208994 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15110101
Food Chem Toxicol.
2004 Jun;42(6):925-33.
Aluminum
fluoride affects the structure and functions of cell membranes.
Suwalsky
M, Norris B, Villena F, Cuevas F, Sotomayor P, Zatta P.
Faculty of Chemical Sciences, University of Concepcion, Casilla
160-C, Concepcion, Chile. msuwalsk@udec.cl
No useful biological function for aluminum has been found. To
the contrary, it might play an important role in several pathologies,
which could be related to its interactions with cell membranes.
On the other hand, fluoride is a normal component of body fluids,
soft tissues, bones and teeth. Its sodium salt is frequently added
to drinking water to prevent dental caries. However, large doses
cause severe pathological alterations. In view of the toxicity
of Al(3+) and F(-) ions, it was thought of interest to explore
the damaging effects that AlF(3) might induce in cell membranes.
With this aim, it was incubated with human erythrocytes, which
were examined by phase contrast and scanning electron microscopy,
and molecular models of biomembranes. The latter consisted of
large unilamellar vesicles (LUV) of dimyristoylphosphatidylcholine
(DMPC) and bilayers of DMPC and dimyristoylphosphatidylethanolamine
(DMPE) which were studied by fluorescence spectroscopy and X-ray
diffraction, respectively. In order to understand the effects
of AlF(3) on ion transport (principally sodium and chloride) we
used the isolated toad skin to which electrophysiological measurements
were applied. It was found that AlF(3) altered the shape of erythrocytes
inducing the formation of echinocytes. This effect was explained
by X-ray diffraction which revealed that AlF(3) perturbed the
structure of DMPC, class of lipids located in the outer monolayer
of the erythrocyte membrane. This result was confirmed by fluorescence
spectroscopy on DMPC LUV. The biphasic (stimulatory followed by
inhibitory) effects on the isolated skin suggested changes in
apical Cl(-) secretion and moderate ATPase inactivation.
PMID:
15110101 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15165836
Neuropharmacology.
2004 Jul;47(1):81-91.
Cannabinoid
signaling in rat cerebellar granule cells: G-protein activation,
inhibition of glutamate release and endogenous cannabinoids.
Breivogel
CS, Walker JM, Huang SM, Roy MB, Childers SR.
Department of Pharmaceutical Sciences, Campbell University School
of Pharmacy, P.O. Box 1090, Buies Creek, NC 27506, USA.
Previous studies have indicated that cannabinoids inhibit presynaptic
neurotransmitter release in brain through CB(1) receptors. To
examine this issue in a primary neuronal culture system, rat cerebellar
granule cells (CGCs) were prepared. [(35)S]GTPgammaS binding assays
in saponin-permeabilized CGCs showed that G-protein activation
by the CB(1) agonist, WIN55212-2, and adenosine A(1) agonist,
phenylisopropyladenosine, was maximal during the second week in
culture. ?(9)-tetrahydrocannabinol stimulated [(35)S]GTPgammaS
binding to a lesser degree than WIN55212-2, and the antagonists
SR141716A and AM281 acted as inverse agonists in intact CGCs,
but not in CGC membrane preparations. Ten micromolar WIN55212-2
and ?(9)-tetrahydrocannabinol decreased depolarization-evoked
efflux of [(3)H]-d-aspartate from CGCs by 32% and 13%, respectively.
SR141716A and AM281 increased [(3)H]-d-aspartate release by 28%.
The fatty acid amide hydrolase (FAAH) inhibitor phenylmethylsulfonyl
fluoride (PMSF) and the anandamide uptake inhibitor AM404 inhibited
transmitter release, implying that the antagonist effects were
mediated by blockade of endocannabinoid activity. Levels of endocannabinoids
(both anandamide and 2-arachidonyl glycerol [2-AG]) in extracts
of the cells and cell incubation buffer were increased by PMSF
pre-treatment. Depolarization with KCl significantly decreased
the amount of anandamide and 2-AG in PMSF-treated CGCs. These
results suggest that endogenous cannabinoids inhibit neurotransmitter
release in CGCs, which may also release endocannabioids upon neural
stimulation.
PMID: 15165836 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15271992
J Biol Chem. 2004
Jul 22 [Epub ahead of print]
Perturbing
the linker regions of the a-subunit of transducin: A new class
of constitutively active GTP-binding proteins.
Majumdar
S, Ramachandran S, Cerione RA.
Department of Molecular
Medicine, Cornell University, Ithaca, NY 14853-6401.
The GDP-GTP exchange
activity of the retinal G protein, transducin, is markedly accelerated
by the photoreceptor rhodopsin in the first step of visual transduction.
The X-ray structures for the alpha subunits of transducin (alpha(T))
and other G proteins suggest that the nucleotide-binding (Ras-like)
domain and a large helical domain form a 'clam shell' that buries
the GDP molecule. Thus, receptor-promoted G protein activation
may involve 'opening the clam shell' to facilitate GDP dissociation.
In this study, we have examined whether perturbing the linker
regions connecting the Ras-like and helical domains of Galpha
subunits gives rise to a more readily exchangeable state. The
sole glycine residues in linkers 1 and 2 were individually changed
to proline residues within an alpha(T)/alpha(i1) chimera (designated
alpha(T)*). Both alpha(T)* linker mutants showed significant increases
in their basal rates of GDP-GTP exchange when compared either
to retinal alpha(T) or recombinant alpha(T)*. The
alpha(T)* linker mutants were responsive to aluminum fluoride
which binds to alpha-GDP complexes and induces changes in Switch
2. While both linker mutants were further activated by
light-activated rhodopsin together with the betagamma complex,
their activation was not influenced by betagamma, alone, arguing
against the idea that the betagamma complex helps to pry apart
the helical and Ras-like domains of Galpha subunits. Once
activated, the alpha(T)* linker mutants were able to stimulate
the cyclic GMP phosphodiesterase. Overall, these findings highlight
a new class of activated Galpha mutants that constitutively exchange
GDP for GTP and should prove valuable in studying different G
protein-signaling systems.
PMID: 15271992
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15209009
Wei Sheng Yan Jiu.
2004 Mar;33(2):211-3.
[Effect
of fluorine, selenium and cadmium on anti-oxidase and microelements
in rat's body]
[Article in Chinese]
Mou S, Qin S, Hu Q, Duan X.
Medicine in Medical School of Hubei Institute for Nationalities,
Enshi 445000, China.
OBJECTIVE: To study the effect of fluorine, selenium and cadmium
on lipid peroxide(LPO), the activity of glutathione peroxidase
(GSH-Px) and microelements such as cadmium, selenium and zinc
in rats.
METHODS: Measurement of the contents of LPO, GSH-Px and microelements
such as cadmium, selenium and zinc in SD rats after killing that
have drunk water containing fluorine, selenium and cadmium eight-week
ago.
RESULTS: The contents of GSH-Px in the serum, liver and kidney
of rats that were contaminated with fluorine, selenium and cadmium
respectively remarkably reduced and the content of LPO noticeably
increased in comparison with those of rats without being contaminated.
The contents of GSH-Px noticeably increased and LPO remarkably
reduced in those contaminated with the combination of any two
of the three elements when compared with those in the rats contaminated
with any one element of them, while the contents of GSH-Px in
those contaminated with the combination of the three elements
increased even more. Excessive selenium or cadmium led to the
increase of selenium content in kidney and cadmium content in
liver by several times. Excessive fluorine
or cadmium gave rise to the lack of selenium and zinc.
Selenium brought out universal increase of zinc in liver and kidney.
The combination of fluorine and selenium
or the combination of cadmium and selenium or that of fluorine,
selenium and cadmium produced remarkable decrease of the accumulation
of selenium in kidney and cadmium in liver. They also lowed the
loss of zinc caused by fluorine or cadmium.
CONCLUSION: Excessive fluorine, selenium or cadmium could inhabit
the activity of GSH-Px in rats, which could diminish the antioxidation
ability of the body. But when two or three of the chemical elements
coexisted, they reduced the inhabitation of each of them on the
activity of GSH-Px and in the meantime decreased the accumulation
of cadmium and selenium and diminished the loss of zinc caused
by fluorine and cadmium.
PMID: 15209009 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15121184
Mol Cell Neurosci.
2004 May;26(1):123-134.
Gating
and modulation of presumptive Na(V)1.9 channels in enteric and
spinal sensory neurons.
Coste
B, Osorio N, Padilla F, Crest M, Delmas P.
Integration des Informations Sensorielles, CNRS, UMR 6150, Faculte
de Medecine, IFR Jean Roche, 13916 Marseille Cedex 20, France.
The Na(V)1.9 subunit is expressed in nociceptive dorsal root ganglion
(DRG) neurons and sensory myenteric neurons in which it generates
'persistent' tetrodotoxin-resistant (TTX-R) Na(+) currents of
yet unknown physiological functions. Here, we have analyzed these
currents in details by combining single-channel and whole-cell
recordings from cultured rat DRG and myenteric neurons. Comparison
of single-channel with whole-cell data indicates that recording
using internal CsCl best reflects the basic electrical features
of Na(V)1.9 currents. Inclusion of fluoride in the pipette solution
caused a negative shift in the activation and inactivation gates
of Na(V)1.9 but not Na(V)1.8. Fluoride acts
by promoting entry of Na(V)1.9 channels into a preopen closed
state, which causes a strong bias towards opening and enhances
the ability of sensory neurons to sustain spiking. Thus,
the modulation of the resting-closed states of Na(V)1.9 channels
strongly influences nociceptor excitability and may provide a
mechanism by which inflammatory mediators alter pain threshold.
PMID: 15121184 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15104114
Toxicol Lett. 2004
Mar 7;147(3):229-35.
Zinc
protection from fluoride-induced testicular injury in the bank
vole (Clethrionomys glareolus).
Krasowska
A, Wlostowski T, Bonda E.
Institute of Biology, University of Bialystok, Swierkowa 20B,
15-950 Bialystok, Poland. alak@uwb.edu.pl
Previous work has shown that a high fluoride intake in rodents
leads to histopathological changes in the germinal epithelium
of testes that is associated with zinc deficiency. The purpose
of this study was to determine whether supplemental dietary Zn
would protect against testicular toxicity induced by fluoride
in a small rodent, the bank vole. The 4-month
exposure period to fluoride (200 microg/ml of drinking water)
induced histopathological changes (hemorrhage in interstitium,
necrosis and apoptosis in seminiferous tubule epithelium) which
were accompanied by decreased testicular zinc concentration and
increased lipid peroxidation. Supplemental dietary zinc
(110-120 microg/g) together with fluoride treatment resulted in
complete reversal of the fluoride-mediated effects. However,
supplemented dietary Zn did not affect the accumulation of fluoride
in the testes and bone. These data suggest that a zinc-enriched
diet protects seminiferous
tubules against fluoride toxicity by preventing the fluoride-induced
testicular zinc deprivation.
PMID: 15104114 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15103674
Phytother Res. 2004
Mar;18(3):244-6.
The
effect of Pycnogenol on fluoride induced rat kidney lysosomal
damage in vitro.
Arhima
MH, Gulati OP, Sharma SC.
Department of Pharmacology and Therapeutics, Trinity College,
Dublin 2, Ireland.
Pycnogenol (PYC) is a procyanidin-rich extract of the bark of
French maritime pine (Pinus pinaster) with a potent ability to
scavenge free radicals. Lysosome-rich fractions from rat renal
cortices were incubated with varying amounts of PYC and challenged
with noxious doses of fluoride. Controls were also included. The
release of N-acetyl-beta-d-glucosaminidase (NAG) isozymes in the
supernatant was estimated by spectrophotometric methods. The protein
content of the renal cortex was also determined. Our
results show that fluoride in unhealthy doses can cause a concentration
dependent release of N-acetyl-beta-d-glucosaminidase (NAG) isozymes
from the renal lysosomes. This may be related to its known
ability to initiate free radical formation or direct damaging
effects on the lysosomal membrane. As a blend of bio flavonoids
pycnogenol has a potent ability to scavenge free radicals. In
our study PYC was effective in preventing fluoride induced release
of NAG isozymes from the renal lysosomes. Copyright 2004 John
Wiley & Sons, Ltd.
PMID: 15103674 [PubMed - in process]
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15225605
FEBS Lett. 2004
Jul 2;569(1-3):37-42.
Fluoride
curcumin derivatives: new mitochondrial uncoupling agents.
Ligeret
H, Barthelemy S, Bouchard Doulakas G, Carrupt PA, Tillement JP,
Labidalle S, Morin D.
Laboratoire de Pharmacologie Creteil, France.
The mitochondrial effects of two fluoride curcumin derivatives
were studied. They induced the collapse of mitochondrial membrane
potential ( [Formula: see text] ), increased mitochondrial respiration,
and decreased O(2) [Formula: see text] production and promoted
Ca(2+) release. These effects were reversed by the recoupling
agent 6-Ketocholestanol, but not by cyclosporin A, an inhibitor
of the permeability transition pore (PTP), suggesting that these
compounds act as uncoupling agents. This idea was reinforced by
the analysis of the physico-chemical properties of the compounds
indicating, that they are mainly in the anionic form in the mitochondrial
membrane. Moreover, they are able to induce PTP opening by promoting
the oxidation of thiol groups and the release of cytochrome c,
making these two molecules potential candidates
for induction of apoptosis.
PMID: 15225605 [PubMed - in process]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14728983&dopt=Abstract
