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Research ArticleArticle

The Role of Src Kinase in the Potentiation by Ethanol of Cytokine- and Endotoxin-Mediated Nitric Oxide Synthase Expression in Rat Hepatocytes

Min-Liang Kuo, Yat-Pang Chau, Jyh-Horng Wang and Pei-Jung Lin
Molecular Pharmacology September 1997, 52 (3) 535-541; DOI: https://doi.org/10.1124/mol.52.3.535
Min-Liang Kuo
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Yat-Pang Chau
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Jyh-Horng Wang
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Pei-Jung Lin
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Abstract

This study demonstrates that exposure of primary rat hepatocytes or mouse BNL Cl.2 liver cell line to ethanol causes potentiation of tumor necrosis factor-α (TNF-α)- and lipopolysaccharide (LPS)-stimulated nitrite accumulation. The potentiating effect of ethanol (0.02–2 mm ) appears to be time and concentration dependent. Consistent with nitrite production, the amount of inducible nitric oxide synthase (iNOS) mRNA and protein is initially detected at 4 hr after treatment with TNF-α/LPS/ethanol. Furthermore, the capability of these agents to induce iNOS expression is primarily determined by the age of the animals. Interestingly, antioxidants such asN-acetylcysteine (NAC), ascorbic acid, or α-tocopherol fail to inhibit TNF-α/LPS/ethanol-induced increase in iNOS protein. In addition, several kinase inhibitors, including staurosporine, genistein, curcumin, and herbimycin A, were used to examine their effects on this induction. Among them, only herbimycin A potently inhibits the accumulation of nitrite and iNOS expression. In vitro kinase assay verifies that Src tyrosine kinase is rapidly activated with a peak at 1 hr after treatment with TNF-α/LPS/ethanol but is not activated by these agents singly or doubly. As expected, herbimycin A can block Src kinase activity under circumstances in which iNOS expression is also inhibited. However, our results do not indicate that the mitogen-activated protein kinase is activated after treatment with these agents. The study results suggest that Src tyrosine kinase plays a prominent role in transducing the signal to induce iNOS expression in hepatocytes treated with TNF-α/LPS/ethanol.

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Molecular Pharmacology: 52 (3)
Molecular Pharmacology
Vol. 52, Issue 3
1 Sep 1997
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Research ArticleArticle

The Role of Src Kinase in the Potentiation by Ethanol of Cytokine- and Endotoxin-Mediated Nitric Oxide Synthase Expression in Rat Hepatocytes

Min-Liang Kuo, Yat-Pang Chau, Jyh-Horng Wang and Pei-Jung Lin
Molecular Pharmacology September 1, 1997, 52 (3) 535-541; DOI: https://doi.org/10.1124/mol.52.3.535

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Research ArticleArticle

The Role of Src Kinase in the Potentiation by Ethanol of Cytokine- and Endotoxin-Mediated Nitric Oxide Synthase Expression in Rat Hepatocytes

Min-Liang Kuo, Yat-Pang Chau, Jyh-Horng Wang and Pei-Jung Lin
Molecular Pharmacology September 1, 1997, 52 (3) 535-541; DOI: https://doi.org/10.1124/mol.52.3.535
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