Secretory sphingomyelinase

Several physiologic and pathophysiologic processes in which sphingomyelinas es (SMases) have been implicated may involve extracellular sphingomyelin (S M) hydrolysis. A candidate enzyme for these processes is a recently discove red SMase called secretory SMase, or S-SMase. S-SMase arises from the acid sphingomyelinase (ASM) gene via differential protein trafficking of a commo n 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 a mounts of the enzyme, is partially Zn2+-independent. S-SMase functions best at acid pH but can hydrolyze certain physiologic substrates, such as ather ogenic lipoproteins, at neutral pH. In endothelial cells, the secretion of S-SMase is regulated at the level of protein trafficking by inflammatory cy tokines. Current work implicates a role for S-SMase in atherogenesis, and f uture 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. (C) 1999 Elsevier Science Ireland Ltd. All rights re served.