Induction of hepatic inducible nitric oxide synthase by cholesterol in vivo and in vitro

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Title
Induction of hepatic inducible nitric oxide synthase by cholesterol in vivo and in vitro
Author(s)
Jun Woo Kim; Keon Wook Kang; Goo Taeg Oh; Ji Hyun Song; Nak Doo Kim; Young Mi Kim Pak
Bibliographic Citation
Experimental and Molecular Medicine, vol. 34, no. 2, pp. 137-144
Publication Year
2002
Abstract
Cholesterol-rich diet impairs endothelial NO synthase (eNOS) and enhances inducible NOS (iNOS) expression. In this study, we investigated effects of cholesterol on iNOS expression in high-fat-fed rat models, HepG2 and RAW264.7 cells. The high-fat diet increased the plasma total cholesterol level 6-7 fold and low-density lipoprotein cholesterol level (LDL-C) approximately 70 fold and slightly increased the level of lipid peroxidation as determined by thiobarbituric acid-reactive substance assay. The high-fat diet also increased plasma nitric oxide (NO) concentrations up to 5 fold, and induced iNOS mRNA expression in liver. The contractile responses of the endothelium-denuded thoracic aortic rings to phenylephrine were significantly damaged in high-fat-fed rats when assessed by organ chamber study. Treatment with estrogen for 4 days failed to reduce iNOS expressions as well as aortic contractility, although it improved lipid profiles. In cultured HepG2 or murine macrophage RAW264.7 cells, 3 days treatment with either 25-hydroxycholesterol or 7-ketocholesterol induced iNOS mRNA expression, as determined by RT-PCR. Our data suggested that the chronic exposure of hepatocytes and macrophage cells to high concentration of cholesterol or oxysterols may induce iNOS expression and subsequent synthesis of NO, which may be important in the pathogenesis of atherosclerosis.
Keyword
cholesterolexpressionHepG2iNOS
ISSN
I000-0028
Publisher
Springer-Nature Pub Group
DOI
http://dx.doi.org/10.1038/emm.2002.20
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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