Inhibition of the Neutral Magnesium-dependent Sphingomyelinase by Glutathione *

摘要: Sphingomyelin hydrolysis through the activation of sphingomyelinases has become a potentially important signaling pathway with product ceramide implicated in regulation cell growth, differentiation, apoptosis, and inflammatory responses. However, little is known about sphingomyelinases. In this study, we show that magnesium-dependent, neutral pH-optimum membrane-associated sphingomyelinase (N-SMase) inhibited, dose-dependent manner, by glutathione (GSH) at physiological concentrations greater than 95% inhibition observed 5 mM GSH. The inhibitory effect GSH was reproduced gamma-glutamyl-cysteine, but not cysteinyl-glycine fragment S-modified analogs were as effective inhibiting N-SMase. On other hand, neither dithiothreitol nor beta-mercaptoethanol had any on N-SMase, suggesting sulfhydryl required for no acid SMase, whereas inhibited SMase. These results suggest cells N-SMase inactive presence (1-20 mM). Finally, treatment cultured Molt-4 synthesis inhibitor, L-buthionine-(SR)-sulfoximine, resulted time-dependent depletion GSH, accompanied an increased sphingomyelin production ceramide. Since variety process cellular injury these studies may be mechanism This therefore bring together fields oxidative stress products hydrolysis.