4-hydroxynonenal prevents NO production in vascular smooth muscle cells byinhibiting nuclear factor-kappa B-dependent transcriptional activation of inducible NO synthase

Citation
Y. Hattori et al., 4-hydroxynonenal prevents NO production in vascular smooth muscle cells byinhibiting nuclear factor-kappa B-dependent transcriptional activation of inducible NO synthase, ART THROM V, 21(7), 2001, pp. 1179-1183
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN journal
1079-5642 → ACNP
Volume
21
Issue
7
Year of publication
2001
Pages
1179 - 1183
Database
ISI
SICI code
1079-5642(200107)21:7<1179:4PNPIV>2.0.ZU;2-5
Abstract
The role of lipid peroxidation products in atherogenesis was studied. We in vestigated whether 4-hydroxy-2-nonenal (HNE) modulates activation of the nu clear factor (NF)-kappaB system or alters expression of the NF-kappaB targe t gene product, inducible NO synthase (iNOS), in vascular smooth muscle cel ls (VSMCs) stimulated by lipopolysaccharide (LPS) in combination with inter feron (IFN)-gamma (LPS/IFN). NO production induced by LPS/IFN was dose-depe ndently inhibited by HNE. NF-kappaB activation by LPS/IFN was inhibited by HNE in a dose-dependent manner. HNE significantly decreased LPS/IFN-stimula ted proteolysis of I kappaB-alpha. iNOS promoter activity stimulated by LPS /IFN was also decreased by HNE dose-dependently. The treatment of VSMCs wit h LPS/IFN strongly stimulated iNOS mRNA and protein expression. The LPS/IFN -induced increases in iNOS mRNA and protein levels were dose-dependently de creased by HNE, Our data suggest that treatment with HNE blocks signaling e vents required for I kappaB-alpha degradation, thereby preventing NF-kappaB activation. Inhibition of NF-kappaB-regulated gene expression, especially modulation of NO production, may contribute to atherogenesis.