Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide stimulates in vitro the synthesis of glutathione, an abundant thiol with a number of functions such as detoxification of xenobiotics and reactive oxygen species. In order to study this relationship in an animal model of hypertension, we treated spontaneously hypertensive rats (SHR) either with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) or with a nitric oxide donor isosorbide-5-mononitrate (IS-5-MN). Inhibition of nitric oxide synthesis led to malignant hypertension and to a marked decrease in glutathione synthesis through down-regulation of the rate-limiting enzyme gamma-glutamylcysteine synthetase (GCS). The reduction in GCS activity was further augmented in SHR on a high sodium diet. Renal GCS activity in untreated SHR was 234 +/- 14 and 240 +/- 18 nmol/min/mg protein (mean +/- SD) on a low and high sodium diet, respectively. When L-NAME was included in the diet, the activities dropped to 173 +/- 28 and 123 +/- 28 for the low and high sodium diets, respectively. IS-5-MN attenuated the rise in blood pressure induced by sodium chloride, but did not affect the GCS activity. The mechanism of GCS stimulation by nitric oxide is not known, but our results combined with the literature suggest that a relatively high concentration of nitric oxide is needed.
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PMID:Down-regulation of renal glutathione synthesis by systemic nitric oxide synthesis inhibition in spontaneously hypertensive rats. 1064 53

We investigated the role of glutathione and nitric oxide synthase (NOS) in fiber-induced cell and DNA toxicity using alkaline (pH 13) single-cell gel electrophoresis (the Comet assay). Transformed cultured human pleural mesothelial (MeT-5A) cells and alveolar epithelial cells (A549) were exposed to crocidolite asbestos fibers (1-10 microg/cm(2)) in the presence of buthionine sulfoximine (BSO) or L-arginine-methyl ester (L-NAME). BSO inhibits gamma-glutamylcysteine synthetase (gamma-GCS) and causes glutathione depletion, and L-NAME inhibits nitric oxide generation. Studies were also conducted to assess the expression of the heavy and light subunits of gamma-GCS in human pleural mesothelium and bronchial epithelium in vivo and the induction of inducible NOS (iNOS) by asbestos fibers. Asbestos fibers caused DNA single-strand breaks, and the process was significantly enhanced by BSO (69% compared to the non-treated cells). A549 cells had a 3.5-fold glutathione content compared to MeT-5A cells, which was consistent with the higher resistance of these cells against oxidants and fibers. Flow cytometry of iNOS showed no change of iNOS by the fibers in either cell type in vitro. L-NAME had no effects on the DNA single-strand breaks in the Comet assay, either. Studies on lung biopsies showed that the immunoreactivities of both gamma-GCS subunits were very low in healthy human mesothelium in vivo. We conclude that glutathione may play an essential role in protecting intact cells against fiber-induced oxidative DNA alterations, and low gamma-GCS reactivity in pleural mesothelium may be associated with the high sensitivity of mesothelial cells to fiber-induced toxicity.
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PMID:Modulation of DNA single-strand breaks by intracellular glutathione in human lung cells exposed to asbestos fibers. 1181 40

We examined whether nitric oxide (NO) in vivo could induce interscapular brown adipose tissue (IBAT) glutathione synthesis. Data show that NO induces in vivo IBAT glutathione synthesis through activation of glutamate-cysteine ligase (GCL) mRNA and protein expression. This NO effect appeared to be mediated by nuclear factor-kappaB (NF-kappaB) activation. We have also observed a complex series of in vivo cellular responses during chronic inhibition of NO synthesis, suggesting that regulatory pathways unrelated to GCL alteration underlie glutathione level increase induced by N(omega)-nitro-l-arginine methyl ester (l-NAME). In general, glutathione synthesis in IBAT seemed to be finely tuned by NO to provide glutathione for either mediating the effects of NO, or for preventing potential nitrosative stress.
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PMID:l-Arginine supplementation induces glutathione synthesis in interscapular brown adipose tissue through activation of glutamate-cysteine ligase expression: The role of nitric oxide. 1963 Nov 98