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Effects
of aluminum exposure on glutamate metabolism: A possible explanation for
its toxicity.
Struys-Ponsar C, Guillard O, van den Bosch de Aguilar P
Laboratoire de Biologie Cellulaire, Batiment Carnoy, 5 place Croix du Sud,
Louvain-la-Neuve, B. 1348, Belgium. Medline
The effects of aluminum (Al) exposure on glutamate metabolism were investigated
to study the mechanism of Al toxicity in rat brain. In astrocytes, the
glutamate-glutamine pathway prevents the accumulation of the excitatory
neurotransmitter glutamate, recognized as a neuronal excitotoxin when present in
excess in the extracellular space. Changes in the level of l-aspartate,
l-glutamate, and its metabolite l-glutamine were investigated in various regions
of rat brains following intraperitoneal injection of aluminium gluconate for 2
months. The changes observed were area- and amino-acid-specific. An increase in
glutamine, but not in l-glutamate or l-aspartate, was noted in the hippocampus
and neocortex of Al-treated rats. This increase in vivo was consistent with
observations in vitro. Exposure of cultured astrocytes to Al chloride (200, 400,
and 800 &mgr;M) specifically increased glutamine synthetase activity for the
three concentrations tested. In parallel with this increase, a higher rate of
disappearance of glutamate from culture medium was observed during the first 10
min of incubation for the three concentrations tested, as well as an
accumulation of glutamine in the cellular extract after 30 min. These
observations indicate that the astrocyte population is a potential target for Al
toxic action that could mediate the pathogenesis of this metal. Copyright 2000
Academic Press.
PMID: 10785454, UI: 20249085
Inhibitory
effect of Ginkgo biloba extract on the expression of inducible nitric oxide
synthase in endothelial cells
Cheung
F; Siow YL; Chen WZ; O K
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Biochem
Pharmacol; 58(10):1665-73, 1999 Nov 15. - Medline
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Excessive
production of nitric oxide (NO) may have cytotoxic effects through the formation
of peroxynitrite with superoxide. The extract of Ginkgo biloba leaves (EGb) has
been demonstrated to be a potent scavenger of free radicals. Although EGb has
been shown recently to inhibit NO production in macrophages, its effect on NO
production in endothelial cells is largely unknown. The objective of this study
was to elucidate the mechanism by which EGb affects NO production in a human
endothelial cell line (ECV304). After cells were incubated with EGb (10-100
microg/mL) for 2 or 4 hr, the amounts of NO metabolites released by the cells
were quantitated, and cellular NOS activities were determined following the
conversion of [3H]arginine to [3H]citrulline. NOS protein expression was
determined by western immunoblotting analysis. mRNA levels were examined by
reverse transcription-polymerase chain reaction (RT-PCR) analysis. EGb (50
microg/mL) caused a 30% reduction of NO metabolites released by endothelial
cells. Following EGb treatment, cellular inducible NO synthase (iNOS) activity
was reduced by 28% with a concomitant reduction in the levels of iNOS protein
mass and mRNA. There was no change in the activity or protein mass of
constitutive NO synthase in these cells. EGb inhibited NO production by
attenuating the level of iNOS mRNA in ECV304 cells. Selective inhibition of iNOS
by EGb may be therapeutically relevant in modulating NO production in
endothelial cells (Au)
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