Secretory sphingomyelinase.
Several physiologic and pathophysiologic processes in which sphingomyelinases (SMases) have been implicated may involve extracellular sphingomyelin (SM) hydrolysis. A candidate enzyme for these processes is a recently discovered SMase called secretory SMase, or S-SMase. S-SMase arises from the acid sphingomyelinase (ASM) gene via differential protein trafficking of a common protein precursor; this precursor can be targeted to either lysosomes or the Golgi secretory pathway. S-SMase is activated by physiologic levels of Zn2+, although the S-SMase from endothelial cells, which secrete abundant amounts of the enzyme, is partially Zn2+-independent. S-SMase functions best at acid pH but can hydrolyze certain physiologic substrates, such as atherogenic lipoproteins, at neutral pH. In endothelial cells, the secretion of S-SMase is regulated at the level of protein trafficking by inflammatory cytokines. Current work implicates a role for S-SMase in atherogenesis, and future work will be directed at understanding the potential roles of S-SMase in other processes, such as ceramide-mediated cell-signaling and the host inflammatory response.
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Department of Medicine, Columbia University, New York, NY 10032, USA. iat1@columbia.edu
D000818:Animals; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism / Q000502:physiology*
D007527:Isoenzymes; D013108:Sphingomyelin Phosphodiesterase