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
收藏
页码：757 / 763
页数：7
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