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Involvement of nitric oxide in the promotion of cell survival by ceramide 1-phosphate |
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| Authors: | Gangoiti Patricia Granado Maria H Arana Lide Ouro Alberto Gómez-Muñoz Antonio |
| Institution: | Department of Biochemistry and Molecular Biology, University of the Basque Country, Bilbao, Spain. |
| Abstract: | 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. |
| Keywords: | A-SMase acid sphingomyelinase BMDM bone marrow-derived macrophages C1P ceramide-1-phosphate C2- acetyl C8- octanoyl CAPE caffeic acid phenylethyl ester DTT diethyltreitol FBS fetal bovine serum 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-sulphophenyl)-2H-tetrazolium inner salt] L-NAME l-nitroarginine methyl ester" target="_blank">l-nitroarginine methyl ester L-NIL l-lysine" target="_blank">N-iminoethyl-l-lysine NO nitric oxide NOS nitric oxide synthase PBS phosphate-buffered saline PI3-K phosphatidylinositol 3-kinase TBS Tris-buffered saline TLC thin layer chromatography |
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