期刊
TOXICOLOGY AND APPLIED PHARMACOLOGY
卷 217, 期 2, 页码 176-184出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.taap.2006.08.010
关键词
heme oxygenase-1; ischemic/reperfusion; vascular smooth muscle cell; nitric oxide; preconditioning
Nitric oxide (NO) signaling pathways are important in both the maintenance of vascular homeostasis and disease progression. Overproduction of NO has been associated with ischernia/reperfusion (I/R) injury. Growing evidences suggest that NO preconditioning has cytoprotective effects against I/R injury. However, the mechanism with which NO mediates these effects remains to be elucidated. The purpose of this study was to examine the mechanism of how NO preconditioning inhibits subsequent NO-induced apoptosis in vascular smooth muscle cells (VSMC), specifically focusing on heme oxygenase-1 (HO-1). According to our data, sodium nitroprusside (SNP) increased HO-1 expression in a concentration dependent manner. Preconditioning with low concentration SNP (0.3 mM) inhibited subsequent high concentration SNP (1.5 mM)induced apoptosis, and this effect was reversed by the HO-1 inhibitor SnPP. Low concentration SNP-mediated protection involved p38 kinase inactivation and increased Bel-2 expression. Furthermore, mitochondrial membrane potential was concomitantly increased with decreased expressions of Bax, Apaf-1, and activity of caspase-3, which was reversed by SnPP treatment. Our results show that low concentration SNP preconditioning suppresses subsequent high concentration SNP-induced apoptosis by inhibiting p38 kinase and mitochondrial death pathway via HO-1-dependent mechanisms in VSMC. (c) 2006 Elsevier Inc. All rights reserved.
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