Involvement of nitric oxide in the promotion of cell survival by ceramide 1-phosphate.
Macrophages play vital roles in inflammatory responses, and their number at sites of inflammation is strictly regulated by cell death and division. Here, we demonstrate that production of nitric oxide (NO) is a major mechanism whereby ceramide-1-phosphate (C1P) blocks apoptosis in macrophages. However, NO failed to stimulate macrophage proliferation. The prosurvival effect of C1P was blocked by inhibitors of inducible NO synthase. The antiapoptotic effect of C1P was also blocked by phosphatidylinositol 3-kinase or nuclear factor-kappa B inhibitors. Moreover, NO reversed the inhibitory effect of C1P on acid sphingomyelinase, but the prosurvival effect of C1P was independent of this action.
Department of Biochemistry and Molecular Biology, University of the Basque Country, Bilbao, Spain.
Patricia
P
Gangoiti
Maria H
MH
Granado
Lide
L
Arana
Alberto
A
Ouro
Antonio
A
Gómez-Muñoz
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival; D002518:Ceramides / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors
D002518:Ceramides; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; C065576:ceramide 1-phosphate