Preconditioning with low concentration NO attenuates subsequent NO-induced apoptosis in vascular smooth muscle cells via HO-1-dependent mitochondrial death pathway

Journal Article · Fri Dec 01 00:00:00 EST 2006 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.08.010· OSTI ID:20850491

Kwak, Hyun-Jeong ^[1]; Park, Kyoung-Mi ^[1]; Lee, Seahyoung ^[2]; Lim, Hyun-Joung ^[1]; Go, Sang-Hee ^[1]; Eom, Sang-Mi ^[1]; Park, Hyun-Young ^[1]

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1. Division of Cardiovascular Diseases, Center for Biomedical Sciences, National Institutes of Health, Nokbun-dong, Eunpyung-gu, Seoul 122-701 (Korea, Republic of)
2. BK21 Project of Medicinal Science, Yonsei University (Korea, Republic of)

Nitric oxide (NO) signaling pathways are important in both the maintenance of vascular homeostasis and disease progression. Overproduction of NO has been associated with ischemia/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 Bcl-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.

• OSTI ID: 20850491
• Journal Information: Toxicology and Applied Pharmacology, Vol. 217, Issue 2; Other Information: DOI: 10.1016/j.taap.2006.08.010; PII: S0041-008X(06)00300-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
DEATH
HEME
HOMEOSTASIS
INACTIVATION
INJURIES
ISCHEMIA
MEMBRANES
MUSCLES
NITRIC OXIDE
SODIUM