Involvement of nitric oxide in the promotion of cell survival by ceramide 1-phosphate

FEBS Lett. 2008 Jun 25;582(15):2263-9. doi: 10.1016/j.febslet.2008.05.027. Epub 2008 May 27.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Cell Survival
  • Ceramides / pharmacology
  • Ceramides / physiology*
  • Female
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred Strains
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors

Substances

  • Ceramides
  • NF-kappa B
  • Phosphoinositide-3 Kinase Inhibitors
  • ceramide 1-phosphate
  • Nitric Oxide
  • Nitric Oxide Synthase Type II