Sphingosine‐1‐phosphate inhibits acid sphingomyelinase and blocks apoptosis in macrophages

FEBS Letters

Kong, Jennifer²  Steinbrecher, Urs P²  Salh, Bill²  Gómez-Muñoz, Antonio¹ 

[1] Department of Biochemistry and Molecular Biology, University of the Basque Country, P.O. Box 644, 48080 Bilbao, Spain;Department of Medicine, University of British Columbia, Vancouver, BC, Canada

关键词: Sphingosine-1-phosphate;    Sphingomyelinase;    Ceramide;    Apoptosis;    Protein kinase B;    Macrophage;    BMDM;    bone marrow-derived macrophages;    FBS;    fetal bovine serum;    LPA;    lysophosphatidic acid;    M-CSF;    macrophage colony stimulating factor;    MAPK;    mitogen-activated protein kinase;    ERK;    extracellular regulated kinase;    MEK;    MAPK/ERK kinase;    MTS;    3-(4;    5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium;    inner salt;    PI3-K;    phosphatidylinositol 3-kinase;    PKB;    protein kinase B;    Sph-1-P;    sphingosine-1-phosphate;   

DOI  :  10.1016/S0014-5793(03)00197-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown