| Literature DB >> 17257585 |
Aida Abate1, Hui Zhao, Ronald J Wong, David K Stevenson.
Abstract
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-1 promoter by binding Bach1, but also by accelerating Bach1 degradation.Entities:
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Year: 2007 PMID： 17257585 PMCID： PMC1805812 DOI： 10.1016/j.bbrc.2007.01.050
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575