Inhibition of cisplatin-induced nephrotoxicity in rats by buthionine sulfoximine, a glutathione synthesis inhibitor

1987 ◽  
Vol 20 (3) ◽  
pp. 207-210 ◽  
Author(s):  
Robert D. Mayer ◽  
Kan-ei Lee ◽  
Abraham T. K. Cockett
Keyword(s):  
Buthionine Sulfoximine ◽  
Synthesis Inhibitor ◽  
Glutathione Synthesis

Interactions of nitroglycerin and sulfhydryl-donating compounds in coronary microvessels

1994 ◽  
Vol 266 (1) ◽  
pp. H291-H297 ◽  
Author(s):  
R. M. Wheatley ◽  
S. P. Dockery ◽  
M. A. Kurz ◽  
H. S. Sayegh ◽  
D. G. Harrison
Keyword(s):  
Redox Potential ◽  
Potent Inhibitor ◽  
Buthionine Sulfoximine ◽  
Glutathione Synthesis ◽  
Endothelin 1 ◽  
Intracellular Glutathione ◽  
Enzymatic Bioconversion

Previous studies have shown the effect of nitroglycerin on coronary microvessels < 100 microns in diameter is markedly enhanced by L-cysteine. These studies were performed to examine the mechanisms responsible for this effect. Under control conditions, nitroglycerin caused potent dilations of large (> 200 microns diam) coronary microvessels while having minimal effects on small (< 100 microns diam) coronary microvessels [peak relaxations 85 +/- 4 vs. 23 +/- 3% (mean +/- SE) of endothelin-1-constricted vessels, respectively]. L-Cysteine (100 microM) and N-acetylcysteine (100 microM) markedly enhanced nitroglycerin-induced relaxations of small coronary microvessels (peak relaxation 84 +/- 6 and 87 +/- 12%, respectively) while having no effect on relaxations of vessels > 100 microns. In contrast, neither L-methionine (100 microM) nor glutathione (100 microM) enhanced nitroglycerin's vasodilation of small coronary microvessels. The effects of L-cysteine and N-acetylcysteine on the augmentation of nitroglycerin vasodilatation in smaller coronary microvessels was abolished in the presence of buthionine sulfoximine (100 microM), a potent inhibitor of intracellular glutathione synthesis. Buthionine sulfoximine had no effect on the vasodilatation produced by nitroprusside. These data demonstrate that, in smaller coronary microvessels, L-cysteine and N-acetylcysteine enhance nitroglycerin-induced vasodilatation by increasing intracellular glutathione concentrations. Intracellular glutathione, formed from either L-cysteine or N-acetylcysteine, may participate in the formation of an intermediate of nitroglycerin biotransformation or may maintain a redox potential within coronary microvessels that favors enzymatic bioconversion of nitroglycerin.

Glutathione modulates toxic oxygen metabolite injury of canine chief cell monolayers in primary culture

1988 ◽  
Vol 254 (1) ◽  
pp. G49-G56 ◽  
Author(s):  
C. E. Olson
Keyword(s):  
Oxidant Stress ◽  
Buthionine Sulfoximine ◽  
Cell Lysis ◽  
Glutathione Depletion ◽  
Glutathione Synthesis ◽  
Chief Cells ◽  
Cell Monolayers ◽  
Lactate Dehydrogenase Release ◽  
Endogenous Antioxidant ◽  
Generating System

Cultured canine gastric chief cells exposed to a toxic oxygen metabolite-generating system (xanthine plus xanthine oxidase) demonstrated minimal cytolysis, suggesting that these cells have important endogenous antioxidant mechanisms. We have quantified the role of glutathione for protection against toxic oxygen metabolites by measuring cell lysis by lactate dehydrogenase release after variable depletion and repletion of cellular glutathione content. In the absence of exogenous oxidant stress, the glutathione content of chief cells can be depleted to less than 0.2 nmol total glutathione/micrograms DNA or 22% of control without cell lysis over 5 h. However, when challenged with the oxygen metabolite-generating system, cytolysis was greatly enhanced by glutathione depletion. Oxygen metabolite-mediated cytolysis after glutathione depletion was inhibited by exogenous catalase, thiourea, and deferoximine, but not superoxide dismutase or mannitol. These data suggested that hydrogen peroxide and hydroxyl radical mediated cytolysis in glutathione-depleted chief cells. If a substrate for glutathione synthesis, N-acetyl-L-cysteine, was provided to the depleted cells for 1 h before challenge with the oxygen radical-generating system, cell lysis was markedly decreased. However, if glutathione synthesis was blocked during the repletion period by buthionine sulfoximine, protection was not restored. The data supported an important role for glutathione as an endogenous antioxidant, which modulated the sensitivity of cultured chief cells to toxic oxygen metabolite injury.

scholarly journals Ascorbate glutathione-dependent H2O2 scavenging is an important process in axillary bud outgrowth in rosebush

2020 ◽  
Vol 126 (6) ◽  
pp. 1049-1062
Author(s):  
Alexis Porcher ◽  
Vincent Guérin ◽  
Françoise Montrichard ◽  
Anita Lebrec ◽  
Jérémy Lothier ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Marker Gene ◽  
Buthionine Sulfoximine ◽  
Direct Consequence ◽  
Axillary Bud ◽  
Transcriptional Level ◽  
Quiescent State ◽  
Synthesis Inhibitor ◽  
Axillary Bud Outgrowth

Abstract Background and Aims Branching is an important mechanism of plant shape establishment and the direct consequence of axillary bud outgrowth. Recently, hydrogen peroxide (H2O2) metabolism, known to be involved in plant growth and development, has been proposed to contribute to axillary bud outgrowth. However, the involvement of H2O2 in this process remains unclear. Methods We analysed the content of H2O2 during bud outgrowth and characterized its catabolism, both at the transcriptional level and in terms of its enzymatic activities, using RT–qPCR and spectrophotometric methods, respectively. In addition, we used in vitro culture to characterize the effects of H2O2 application and the reduced glutathione (GSH) synthesis inhibitor l-buthionine sulfoximine (BSO) on bud outgrowth in relation to known molecular markers involved in this process. Key Results Quiescent buds displayed a high content of H2O2 that declined when bud outgrowth was initiated, as the consequence of an increase in the scavenging activity that is associated with glutathione pathways (ascorbate–glutathione cycle and glutathione biosynthesis); catalase did not appear to be implicated. Modification of bud redox state after the application of H2O2 or BSO prevented axillary bud outgrowth by repressing organogenesis and newly formed axis elongation. Hydrogen peroxide also repressed bud outgrowth-associated marker gene expression. Conclusions These results show that high levels of H2O2 in buds that are in a quiescent state prevents bud outgrowth. Induction of ascorbate–glutathione pathway scavenging activities results in a strong decrease in H2O2 content in buds, which finally allows bud outgrowth.

Metabolism of S-nitrosoglutathione by endothelial cells

2001 ◽  
Vol 281 (1) ◽  
pp. H432-H439 ◽  
Author(s):  
Hong Zeng ◽  
Netanya Y. Spencer ◽  
Neil Hogg
Keyword(s):  
Nitric Oxide ◽  
Cell Culture ◽  
Endothelial Cells ◽  
Buthionine Sulfoximine ◽  
Synthesis Inhibitor ◽  
Aortic Endothelial Cells ◽  
Absolute Dependence ◽  
Major Factors ◽  
Nitrite Nitrate ◽  
A Minor

S-nitrosoglutathione (GSNO) is an inhibitor of platelet aggregation and has also been shown to protect the ischemic heart from reperfusion-mediated injury. Although GSNO is often used in cell culture as a source of nitric oxide, the mechanisms of GSNO metabolism are not well established. We show here that GSNO decomposition by bovine aortic endothelial cells has an absolute dependence on the presence of cystine in the cell culture medium. In addition, GSNO decay is inhibited by diethyl maleate, an intracellular glutathione scavenger, but not by buthionine sulfoximine, a glutathione synthesis inhibitor. This indicates that thiols in general, rather than specifically glutathione, are the major factors that influence GSNO decay. Only 40% of the nitroso group of GSNO could be recovered as nitrite/nitrate, suggesting that the primary route of GSNO decay is reductive and that nitric oxide is only a minor product of GSNO decay. We conclude that the intracellular thiol pool causes the reduction of extracellular disulfides to thiols, which then directly reduce GSNO.

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