Protective role of heme oxygenase-1 in renal ischemia.
Oxidative stress, which has been implicated in the pathogenesis of ischemic renal injury, degrades heme proteins, such as cytochrome P450, and causes the elevation in the level of cellular free heme, which can catalyze the formation of reactive oxygen species. Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme degradation, is induced not only by its substrate, heme, but also by oxidative stress. In various models of oxidative tissue injuries, the induction of HO-1 confers protection on tissues from further damages by removing the prooxidant heme, or by virtue of the antioxidative, antiinflammatory, and/or antiapoptotic actions of one or more of the three products, i.e., carbon monoxide, biliverdin IXalpha, and iron by HO reaction. In contrast, the abrogation of HO-1 induction, or chemical inhibition of HO activity, abolishes its beneficial effect on the protection of tissues from oxidative damages. In this article, we review the protective role of HO-1 in renal ischemic injury, and its potential therapeutic applications. In addition, we summarize recent findings in the regulatory mechanism of ho-1 gene expression.
Takahashi
Toru
T
Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, 700-8558, Japan. takatoru@cc.okayama-u.ac.jp
Morita
Kiyoshi
K
Akagi
Reiko
R
Sassa
Shigeru
S
D058186:Acute Kidney Injury / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006418:Heme / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008565:Membrane Proteins; D018384:Oxidative Stress; D020011:Protective Agents / Q000378:metabolism*
D008565:Membrane Proteins; D020011:Protective Agents; D006418:Heme; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1