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The Effect of Tin‐mesoporphyrin on Bach1 Expression
Author(s) -
Abate Aida,
Zhao Hui,
Wong Ronald J,
Stevenson David K
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1344-a
Tin‐mesoporphyrin (SnMP) is a potent inhibitor of heme oxygenase (HO), and can lower plasma bilirubin levels after the onset of neonatal jaundice. Although SnMP suppresses HO activity, it can also induce the expression of HO‐1 (inducible HO) mRNA and protein by a mechanism that is not fully understood. We, therefore, examined if SnMP‐mediated HO‐1 induction involves derepression of the HO‐1 promoter through an alteration of Bach1 (HO‐1 repressor) expression. 3T3‐HO‐1‐ luc cells, transfected with the 15‐kb mouse HO‐1 promoter fused to the reporter gene luciferase, were incubated with SnMP for 24h. Nuclear and cytosolic fractions were extracted for Western blotting. In the cytosolic fraction, SnMP produced a 15‐fold increase in HO‐1 protein at 20 μM. Bach1 protein decreased 60 and 78% following treatment with 10‐ and 20‐μM SnMP, respectively. Also, a time‐dependent increase in HO‐1 expression correlated with a 50% decrease in Bach1 protein in nuclear extracts. Furthermore, HO‐1 promoter activity and mRNA levels were induced by SnMP as measured by bioluminescence imaging and real‐time RT‐PCR, respectively. In contrast, Bach1 mRNA levels remained unchanged. Thus, we speculate that SnMP‐mediated HO‐1 induction involves derepression of the HO‐1 promoter by altering Bach1 post‐transcriptionally. Studies are underway to elucidate the mechanism by which SnMP attenuates Bach1 levels in the nucleus of cells.