The role of ceramide in the modulation of intracellular Ca2+ levels by interleukin 1 beta in rat cortical synaptosomes.
We recently demonstrated that the pro-inflammatory cytokine, interleukin 1beta (IL-1beta) elevates intracellular free Ca2+ levels ([Ca2+]i) in rat cortical synaptosomes in a manner involving activation of the IL-1 receptor and stimulation of p42 mitogen-activated protein (MAP) kinase. We now report that the effects of IL-1beta on [Ca2+]i are mimicked by the sphingolipid metabolite ceramide. In cortical synaptosomes ceramide elevates [Ca2+]i in a p42 MAP kinase-dependent manner, and we conclude that the effects of IL-1beta on Ca2+ homeostasis involve ceramide as an upstream component of the p42 MAP kinase pathway.
Campbell
V
V
Department of Physiology, Trinity College, Dublin, Ireland. vacmpbll@tcd.ie
Lynch
M A
MA
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002518:Ceramides / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D007375:Interleukin-1 / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism*
D002518:Ceramides; D007375:Interleukin-1; C064769:N-acetylsphingosine; D019950:Mitogen-Activated Protein Kinase 1; D013110:Sphingosine; D002118:Calcium