Transcriptional regulation of the heme oxygenase-1 gene via the stress response element pathway.
The heme oxygenase-1 (HO-1) enzyme catalyzes the rate-limiting reaction in the catabolism of heme yielding products with pleiotropic, but ultimately, cytoprotective activities. High levels of HO-1 are frequently detected in various pathological states and generally in states of cellular oxidative stress. Induction of HO-1, regulated at the level of gene transcription, is essential for manifestation of the enzyme's cytoprotective function. Extensive analysis of the mouse gene, and to a lesser extent of the human gene, has identified a common mechanism the stress response element (StRE)/Nrf2 transcription factor pathway for gene regulation in response to a diverse array of HO-1 inducers including the substrate heme, various environmental and industrial toxins, and plant-derived polyphenolic compounds. In addition to Nrf2 complexes, numerous dimeric transcription factors bind to the StRE, permitting induction, repression and overall fine-tuning of gene activity. In principle, the multiplicity of StRE binding proteins also provides for a range of pharmaceutical targets for controlled production of the potentially therapeutic HO-1 protein.
Alam
J
J
Department of Molecular Genetics, Ochsner Clinic Foundation, New Orleans, LA 70121, USA. jalam@ochsner.org
Cook
J L
JL
D000818:Animals; D001483:Base Sequence; D004268:DNA-Binding Proteins / Q000502:physiology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics* / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D051267:NF-E2-Related Factor 2; D018384:Oxidative Stress / Q000235:genetics*; D020218:Response Elements; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1