Sphingosine-1-phosphate inhibits acid sphingomyelinase and blocks apoptosis in macrophages.
Sphingosine-1-phosphate (Sph-1-P) regulates critical cellular functions including cell proliferation, differentiation, angiogenesis, and cell survival. However, its mechanisms of action are incompletely understood. Here, we show a novel biological effect of Sph-1-P: inhibition of acidic sphingomyelinase (A-SMase) activity in apoptotic bone marrow-derived macrophages. A-SMase catalyzes the conversion of sphingomyelin to ceramides, which are pro-apoptotic. This action of Sph-1-P prevents the accumulation of ceramides and blocks apoptosis, thereby promoting survival of the macrophages.
Gómez-Muñoz
Antonio
A
Department of Biochemistry and Molecular Biology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain. gbpgomua@lg.ehu.es
Kong
Jennifer
J
Salh
Bill
B
Steinbrecher
Urs P
UP
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000166:cytology; D002470:Cell Survival; D002518:Ceramides / Q000378:metabolism; D066298:In Vitro Techniques; D008246:Lysophospholipids; D008264:Macrophages / Q000166:cytology*; D051379:Mice; D013108:Sphingomyelin Phosphodiesterase / Q000037:antagonists & inhibitors*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology*
D002518:Ceramides; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013108:Sphingomyelin Phosphodiesterase; D013110:Sphingosine