Nitric oxide can function as either a killer molecule or an antiapoptotic effector in cardiomyocytes.
Caspase enzymes are a family of cysteine proteases that play a central role in apoptosis. Recently, it has been demonstrated that caspases can be S-nitrosylated and inhibited by nitric oxide (NO). The present report shows that in chick embryo heart cells (CEHC), NO donor molecules such as S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione, spermine-NO or sodium nitroprusside inhibit caspase activity in both basal and staurosporine-treated cells. However, the inhibitory effect of NO donors on caspase activity is accompanied by a parallel cytotoxic effect, that precludes NO to exert its antiapoptotic capability. N-Acetylcysteine (NAC) at a concentration of 10 mM blocks depletion of cellular glutathione and cell death in SNAP-treated CEHC, but it poorly affects the ability of SNAP to inhibit caspase activity. Consequently, in the presence of NAC, SNAP attenuates not only caspase activity but also cell death of staurosporine-treated CEHC. These data show that changes in the redox environment may inhibit NO-mediated toxicity, without affecting the antiapoptotic capability of NO, mediated by inhibition of caspase enzymes. NO may thus be transformed from a killer molecule into an antiapoptotic agent.
Department of Biochemistry 'G. Moruzzi', University of Bologna, Via Irnerio, 48, 40126, Bologna, Italy. cstefan@biocfarm.unibo.it
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Stefanelli
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Pignatti
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Tantini
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Stanic
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Bonavita
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Muscari
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Guarnieri
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Clo
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Caldarera
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D061945:Caspase Inhibitors; D002478:Cells, Cultured; D002642:Chick Embryo; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000196:embryology / Q000502:physiology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D009574:Nitro Compounds / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology
D061945:Caspase Inhibitors; D009574:Nitro Compounds; C110881:S-nitro-N-acetylpenicillamine; C116027:S-nitroglutathione; D009569:Nitric Oxide; D005978:Glutathione; D010396:Penicillamine; D019311:Staurosporine; D000111:Acetylcysteine