Sphingolipids regulate [Mg2+]o uptake and [Mg2+]i content in vascular smooth muscle cells: potential mechanisms and importance to membrane transport of Mg2+.
Sphingolipids have a variety of important signaling roles in mammalian cells. We tested the hypothesis that certain sphingolipids and neutral sphingomyelinase (N-SMase) can regulate intracellular free magnesium ions ([Mg2+]i) in vascular smooth muscle (VSM) cells. Herein, we show that several sphingolipids, including C2-ceramide, C8-ceramide, C16-ceramide, and sphingosine, as well as N-SMase, have potent and direct effects on content and mobilization of [Mg2+]i in primary cultured rat aortic smooth muscle cells. All of these sphingolipid molecules increase, rapidly, [Mg2+]i in these vascular cells in a concentration-dependent manner. The increments of [Mg2+]i, induced by these agents, are derived from influx of extracellular Mg2+ and are extracellular Ca2+ concentration-dependent. Phospholipase C and Ca2+/calmodulin/Ca2+-ATPase activity appear to be important in the sphingolipid-induced rises of [Mg2+]i. Activation of certain PKC isozymes may also be required for sphingolipid-induced rises in [Mg2+]i. These novel results suggest that sphingolipids may be homeostatic regulators of extracellular Mg2+ concentration influx (and transport) and [Mg2+]i content in vascular muscle cells.
Department of Physiology and Pharmacology, Center For Cardiovascular and Muscle Research, The School of Graduate Studies Program in Molecular and Cellular Science, State University of New York, Box 31, SUNY Health Science Center at Brooklyn, 450 Clarkson Ave., Brooklyn, NY 11203, USA.
Tao
T
Zheng
Wenyan
W
Li
Bella T
BT
Altura
Nilank C
NC
Shah
Burton M
BM
Altura
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013107:Sphingolipids / Q000494:pharmacology*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D002121:Calcium Channel Blockers; D002413:Cations, Divalent; D002614:Chelating Agents; D047428:Protein Kinase Inhibitors; D013107:Sphingolipids; D011493:Protein Kinase C; D010738:Type C Phospholipases; D013108:Sphingomyelin Phosphodiesterase; D008274:Magnesium; D002118:Calcium