The role of Bach1 in the induction of heme oxygenase by tin mesoporphyrin.
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.
Abate
Aida
A
Department of Pediatrics, Stanford University School of Medicine, 300 Pasteur Drive, Rm. S-230, Stanford, CA 94305, USA.
Zhao
Hui
H
Wong
Ronald J
RJ
Stevenson
David K
DK
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects* / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008665:Metalloporphyrins / Q000494:pharmacology*; D051379:Mice; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
C486316:Bach1 protein, mouse; D050976:Basic-Leucine Zipper Transcription Factors; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D012333:RNA, Messenger; C055421:tin mesoporphyrin; D006419:Heme Oxygenase (Decyclizing)