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Published Online: 6 October 2004

Regulation of Heme Oxygenase-1 Gene Transcription: Recent Advances and Highlights from the International Conference (Uppsala, 2003) on Heme Oxygenase

Publication: Antioxidants & Redox Signaling
Volume 6, Issue Number 5

Abstract

Recent investigations into the regulation of heme oxygenase-1 gene (hmox-1) transcription have exposed mechanisms of increasing diversity and complexity worthy of a gene whose expression is modulated by a seemingly endless array of physiological, pathophysiological, and nonphysiological agents and conditions. For instance, contrary to initial and prevalent assumptions that inducer-dependent gene stimulation is mediated principally by the positive action of transcription activators, it now appears that such induction may occur secondarily to deactivation of the repressor protein, Bach1. As a further complication, heme and cadmium, two potent inducers of the hmox-1 gene, inhibit Bach1 function by different mechanisms—by inhibition of DNA binding or promotion of nuclear export, respectively. Bach1 also plays a role in signal-dependent hmox-1 gene repression, an increasingly appreciated phenomenon that is manifested in a species- and cell-specific manner. Although extreme concentrations of the heme oxygenase-1 protein resulting from the opposing phenomena of gene activation and repression have physiological consequences, even minor modulation in the level of this enzyme, as elicited by variations in the length of a dinucleotide repeat region within the human hmox-1 promoter, may be of clinical relevance. Finally, mechanistic diversity is also apparent in the type and combination of protein kinase-dependent, signal transduction pathways used during hmox-1 gene activation. Antioxid. Redox Signal. 6, 924–933.

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cover image Antioxidants & Redox Signaling
Antioxidants & Redox Signaling
Volume 6Issue Number 5October 2004
Pages: 924 - 933
PubMed: 15345152

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Published online: 6 October 2004
Published in print: October 2004

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Dr. Jawed Alam
Department of Molecular Genetics, Ochsner Clinic Foundation, 1516 Jefferson Highway, New Orleans, LA 70121
Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, New Orleans, LA 70112.
Kazuhiko Igarashi
Department of Biochemistry, Hiroshima University School of Medicine, Kasumi 1–2-3, Hiroshima 734–8551, Japan.
Stephan Immenschuh
Institut für Klinische Chemie und Pathobiochemie, Justus-Liebig-Universität Giessen, D-35392 Giessen, Germany.
Shigeki Shibahara
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Aoba-ku, Sendai, Miyagi 980–8575, Japan.
Rex M. Tyrrell
Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY U.K., 924.

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