The dual role of S-nitrosoglutathione (GSNO) during thymocyte apoptosis.
Nitric oxide (NO) is known to regulate redox-sensitive signalling pathways in physiology and pathophysiology. Depending on its concentration, the NO-releasing compound S-nitrosoglutathione (GSNO) causes negative and positive regulation of thymocyte apoptosis. At levels below 0.6 mM, GSNO produces deoxyribonucleic acid (DNA) laddering, which is inhibited by activation of protein kinase C (PKC), cycloheximide treatment, and calcium chelation. Higher concentrations of the NO donor (1-2 mM) suppress thymocyte apoptosis initiated by the classical agonist dexamethasone. Inhibition of apoptosis by NO is analogous to the action of the thiol-blocking compound N-ethylmaleimide (NEM) and the glutathione-S-transferase substrate 1-chloro-2,4-dinitrobenzene (CDNB). Inhibition of apoptosis results from thiol modification of critical proteins in response to NO treatment. Depending on the concentration, GSNO can be involved either in toxic or in protective signalling in thymocyte biology.
Sandau
K
K
University of Erlangen-Nürnberg, Faculty of Medicine, Department of Medicine IV-Experimental Division, Germany.
Brüne
B
B
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D004249:DNA Damage; D004137:Dinitrochlorobenzene / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009603:Nitroso Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D026422:S-Nitrosoglutathione; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D004137:Dinitrochlorobenzene; D009603:Nitroso Compounds; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D026422:S-Nitrosoglutathione; D003513:Cycloheximide; D011493:Protein Kinase C; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate; D005033:Ethylmaleimide