Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Clin Biochem Nutr. 2011 Mar;48(2):161-6. doi: 10.3164/jcbn.09-122GFR. Epub 2010 Apr 10.

Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model.

Author information

  • 1Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.

Abstract

Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1(-/-) mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1(-/-) mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1(-/-) mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

KEYWORDS:

heme oxygenase-1; nonalcoholic fatty liver disease; oxidative stress; peroxisome proliferator-activated receptor α; steatohepatitis

PMID:
21373270
[PubMed]
PMCID:
PMC3045690
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for J-STAGE, Japan Science and Technology Information Aggregator, Electronic Icon for PubMed Central
    Loading ...
    Write to the Help Desk