Peroxynitrite induces apoptosis and decline in intracellular free Mg with concomitant elevation in [Ca2+]I in rat aortic smooth muscle cells: possible roles of extracellular and intracellular magnesium ions in peroxynitrite-induced cell death.
The present study demonstrates that exogenous ONOO(-) can result in rapid declines in intracellular free magnesium ions ([Mg(2+)](i)) concomitant with rapid rises in intracellular free calcium ions ([Ca(2+)](i)) and, subsequently, trigger apoptosis but not necrosis in rat aortic SMCs; high [Mg(2+)] significantly attenuates ONOO(-)-induced apoptosis. ONOO(-)-induced apoptosis in vascular SMCs appears to involve activation of Ca(2+)-Mg(2+)-dependent endonucleases and caspase-3. Mg deficiency itself could not induce apoptosis in these SMCs, but it could significantly enhance ONOO(-)-induced apoptosis.
Li
Jianfeng
J
Department of Physiology and Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York 11203-2056, USA.
Li
Wenyan
W
Liu
Weimin
W
Altura
Bella T
BT
Altura
Burton M
BM
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D004720:Endonucleases / Q000187:drug effects / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D030421:Peroxynitrous Acid; D004720:Endonucleases; D053148:Caspase 3; D008274:Magnesium; D002118:Calcium