Y.H. Zeidan and Y.A. Hannun Pages 454 - 466 ( 13 )
One of the most intriguing enzymes of sphingolipid biology is acid sphingomyelinase (ASMase). In a phospholipase C reaction, ASMase catalyzes the cleavage of the phosphocholine head group of sphingomyelin to generate ceramide. Cumulative efforts of various laboratories over the past 40 years have placed ASMase and its product ceramide at the forefront of lipid research. Activation of the ASMase/ceramide pathway is a shared response to an ever-growing list of receptor and non-receptor mediated forms of cellular stress including: death ligands (TNFα, TRAIL, Fas ligand), cytokines (IL-1, IFNγ), radiation, pathogenic infections, cytotoxic agents and others. The strategic role of ASMase in lipid metabolism and cellular stress response has sparked interest in investigatig the molecular mechanisms underlying ASMase activation. In this article, we review the translational role of the ASMase/ceramide pathway and recent advances on its mechanisms of regulation.
Ceramide, sphingomyelinase, protein kinase C, apoptosis, cancer, membranes, sphingolipids
Department of Biochemistry and Molecular Biology, Medical University of South Carolina,175 Ashley Avenue, P.O. Box 250509, Charleston, South Carolina 29425, USA.