The role of Bach1 in ultraviolet A mediated human heme oxygenase 1 regulation in human skin fibroblasts

Chintan M Raval, Julia Li Zhong, Stephen A Mitchell, Rex M Tyrrell

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Abstract

Up-regulation of Heme oxygenase1 (HO-1) by ultraviolet A (UVA) (320–380 nm) irradiation of human skin cells protects them against oxidative stress. The role of Nrf2 in up-regulation of HO-1 and other Phase 2 genes is well established. The mechanism underlying Bach1-mediated HO-1 repression is less well understood although cellular localisation appears to be crucial. Since prolonged HO-1 over-expression is likely to be detrimental, it is crucial that activation of the gene is transient. We now show that UVA irradiation of cultured human skin fibroblasts enhances accumulation of Bach1 mRNA and protein several-fold. Endogenous Bach1 protein accumulates in the nucleus after 8 h and may occupy MARE sites following HO-1 activation thus providing a compensatory mechanism to control HO-1 over-expression. Overexpression of Bach1, together with MafK, represses basal and UVA-mediated HO-1 protein expression whereas silencing of the Bach1 gene by Bach1-specific siRNAs causes robust enhancement of constitutive HO-1 levels. UVA treatment of cells in which Bach1 has been silenced leads to higher levels of induction of the HO-1 protein. Although Bach1 protein is exported from the nucleus 12 h following UVA irradiation, the release of free cellular heme from microsomal heme-containing proteins is immediate rather than delayed. While heme does promote the export of Bach1 via the Crm1/Exportin1 pathway and is involved in the delayed UVA-mediated export of the protein, it is not clear how this occurs
LanguageEnglish
Pages227-236
Number of pages10
JournalFree Radical Biology and Medicine
Volume52
Issue number1
Early online date6 Nov 2011
DOIs
StatusPublished - 1 Jan 2012

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Heme Oxygenase-1
Fibroblasts
Heme
Skin
Proteins
Genes
Irradiation
Up-Regulation
Chemical activation
Oxidative stress
Gene Silencing
Transcriptional Activation
Oxidative Stress
Cells

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The role of Bach1 in ultraviolet A mediated human heme oxygenase 1 regulation in human skin fibroblasts. / Raval, Chintan M; Zhong, Julia Li; Mitchell, Stephen A; Tyrrell, Rex M.

In: Free Radical Biology and Medicine, Vol. 52, No. 1, 01.01.2012, p. 227-236.

Research output: Contribution to journalArticle

Raval, Chintan M ; Zhong, Julia Li ; Mitchell, Stephen A ; Tyrrell, Rex M. / The role of Bach1 in ultraviolet A mediated human heme oxygenase 1 regulation in human skin fibroblasts. In: Free Radical Biology and Medicine. 2012 ; Vol. 52, No. 1. pp. 227-236
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