Ceramide triggers intracellular calcium release via the IP(3) receptor in Xenopus laevis oocytes.
Ceramide, a product of sphingomyelin turnover, is a lipid second messenger that mediates diverse signaling pathways, including those leading to cell cycle arrest and differentiation. The mechanism(s) by which ceramide signals downstream events have not been fully elucidated. Here we show that, in Xenopus laevis oocytes, ceramide-induced maturation is associated with the release of intracellular calcium stores. Ceramide caused a dose-dependent elevation in the second messenger inositol 1,4,5-trisphosphate (IP(3)) via activation of G(q/11)alpha and phospholipase C-betaX. Elevation of IP(3), in turn, activated the IP(3) receptor calcium release channel on the endoplasmic reticulum, resulting in a rise in cytoplasmic calcium. Thus our study demonstrates that cross talk between the ceramide and phosphoinositide signaling pathways modulates intracellular calcium homeostasis.
Kobrinsky
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Molecular Cardiology Program, Division of Cardiology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York 10032, USA.
Spielman
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Rosenzweig
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Marks
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AR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D016922:Cellular Senescence; D002518:Ceramides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019204:GTP-Binding Proteins / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007425:Intracellular Membranes / Q000378:metabolism*; D007527:Isoenzymes / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D054799:Phospholipase C beta; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D010738:Type C Phospholipases / Q000502:physiology; D014982:Xenopus laevis / Q000378:metabolism*
D015220:Calcium Channels; D002518:Ceramides; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007527:Isoenzymes; D018160:Receptors, Cytoplasmic and Nuclear; D010738:Type C Phospholipases; D054799:Phospholipase C beta; D019204:GTP-Binding Proteins; D002118:Calcium