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Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer

Calvisi, Diego Francesco and Ladu, Sara and Hironaka, Koji and Factor, Valentina M. and Thorgeirsson, Snorri S. (2004) Vitamin E down-modulates iNOS and NADPH oxidase in c-Myc/TGF-alpha transgenic mouse model of liver cancer. Journal of Hepatology, Vol. 41 (5), p. 815-822. ISSN 0168-8278. Article.

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DOI: 10.1016/j.jhep.2004.07.030

Abstract

Background/Aims. Co-expression of c-Myc and TGF-α in the mouse liver accelerates hepatocarcinogenesis and enhances DNA damage due to chronic oxidative stress. Dietary supplementation with vitamin E (VE) inhibits hepatocarcinogenesis and reduces chromosomal alterations in the same mice. Here we investigated the sources of reactive oxygen species (ROS) production in c-Myc/TGF-α transgenic mice. Methods. Inducible nitric oxide synthase (iNOS) and NADPH oxidase levels were determined in c-Myc, TGF-α and c-Myc/TGF-α mice by RT-PCR, western blot analysis and immunohistochemistry. Results. iNOS and nitrotyrosines levels were higher in the three transgenic lines when compared with wild-type mice. Preneoplastic and neoplastic lesions from c-Myc, TGF-α and c-Myc/TGF-α transgenic mice displayed upregulation of NADPH oxidase subunits p47-, 67-phox, Rac1, HSP 70, and HO-1. Importantly, dietary supplementation with vitamin E abolished iNOS expression, lowered nitrotyrosines, p47-, p67-phox, and Rac1 levels, and suppressed HSP 70 and HO-1 proteins in c-Myc/TGF-α livers. Conclusions. The results suggest that iNOS and NADPH oxidase are involved in ROS generation during c-Myc/TGF-α hepatocarcinogenesis and are inhibited by VE treatment. The data provide additional evidence for the potential use of VE in treatment of chronic liver diseases and HCC prevention.

Item Type:Article
ID Code:1278
Status:Published
Refereed:Yes
Uncontrolled Keywords:Vitamin E, HCC, iNOS, NADPH oxidase, transgenic mouse models
Subjects:Area 06 - Scienze mediche > MED/04 Patologia generale
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:Elsevier Science
ISSN:0168-8278
Copyright Holders:© 2004 European Association for the Study of the Liver
Deposited On:18 Aug 2009 10:04

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