Sphingosine 1-phosphate attenuates H2O2-induced apoptosis in endothelial cells.
Reactive oxygen species including H(2)O(2) lead vascular endothelial cells (EC) to undergo apoptosis. Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid mediator that elicits various EC responses. We aimed to explore whether and how S1P modulates EC apoptosis induced by H(2)O(2). Treatment of cultured bovine aortic EC (BAEC) with H(2)O(2) (750 microM for 6h) led to DNA fragmentation (ELISA), DNA nick formation (TUNEL staining), and cleavage of caspase-3, key features of EC apoptosis. These responses elicited by H(2)O(2) were alike markedly attenuated by pretreatment with S1P (1 microM, 30 min). H(2)O(2) induced robust phosphorylation of both p38 and JNK MAP kinases. However, pretreatment with S1P decreased phosphorylation of only p38 MAP kinase, but not that of JNK; conversely, an inhibitor of p38 MAP kinase, but not that of JNK, attenuated H(2)O(2)-induced caspase-3 activation. Thus S1P attenuates H(2)O(2)-induced apoptosis of cultured BAEC, involving p38 MAP kinase.
Moriue
Tetsuya
T
Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-Cho, Kita-Gun, Kagawa 761-0793, Japan.
Igarashi
Junsuke
J
Yoneda
Kozo
K
Nakai
Kozo
K
Kosaka
Hiroaki
H
Kubota
Yasuo
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D053938:DNA Fragmentation; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008246:Lysophospholipids / Q000494:pharmacology*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; D013110:Sphingosine