Acid and neutral sphingomyelinases: roles and mechanisms of regulation.
Ceramide, an emerging bioactive lipid and second messenger, is mainly generated by hydrolysis of sphingomyelin through the action of sphingomyelinases. At least two sphingomyelinases, neutral and acid sphingomyelinases, are activated in response to many extracellular stimuli. Despite extensive studies, the precise cellular function of each of these sphingomyelinases in sphingomyelin turnover and in the regulation of ceramide-mediated responses is not well understood. Therefore, it is essential to elucidate the factors and mechanisms that control the activation of acid and neutral sphingomyelinases to understand their the roles in cell regulation. This review will focus on the molecular mechanisms that regulate these enzymes in vivo and in vitro, especially the roles of oxidants (glutathione, peroxide, nitric oxide), proteins (saposin, caveolin 1, caspases), and lipids (diacylglycerol, arachidonic acid, and ceramide).
Marchesini
Norma
N
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, 29425, USA.
Hannun
Yusuf A
YA
D000818:Animals; D002518:Ceramides / Q000096:biosynthesis / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007477:Ions / Q000737:chemistry; D008274:Magnesium / Q000737:chemistry; D011506:Proteins / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism
D002518:Ceramides; D004791:Enzyme Inhibitors; D007477:Ions; D011506:Proteins; D013109:Sphingomyelins; D013108:Sphingomyelin Phosphodiesterase; D008274:Magnesium