The role of Bach1 in the induction of heme oxygenase by tin mesoporphyrin

被引：22

作者：

Abate, Aida ^{[1
]}

Zhao, Hui ^{[1
]}

Wong, Ronald J. ^{[1
]}

Stevenson, David K. ^{[1
]}

机构：

[1] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2007年 / 354卷 / 03期

关键词：

Bach1; heme oxygenase; isozymes; metalloporphyrins; tin mesoporphyrin;

D O I：

10.1016/j.bbrc.2007.01.050

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tin mesoporphyrin (SnMP), a competitive heme oxygenase (HO) inhibitor, also induces HO-1 mRNA and protein expression by a mechanism that is not fully understood. We examined whether the induction by SnMP is mediated by a de-repression of Bach1, a transcription factor that suppresses the HO-1 gene. Incubation of NIH3T3-HO-1-luc cells with SnMP attenuated HO activity with a concomitant increase in HO-1 mRNA and protein and a decrease in Bach1 and HO-2 proteins, which was not due to transcriptional down-regulation, but accelerated protein decay. Similarly, HO-1 protein degradation was increased by SnMP, despite of an elevation in HO-1 transcription. Transfection of Bach1 shRNA in Hepa cells raised basal HO-1 expression significantly, and SnMP treatment further increased HO-1 mRNA. In conclusion, SnMP induces HO-1 expression not only by de-repressing the HO-I promoter by binding Bach1, but also by accelerating Bach1 degradation. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：757 / 763

页数：7

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