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Cytoprotective effects of heme oxygenase in acute renal failure.

AbstractFollowing ischemia, superoxide is produced during the reperfusion phase in various organs. In renal pathophysiology, excess of free heme, which is released from hemeproteins under these conditions, catalyzes the formation of further reactive oxygen species to accelerate cellular injuries. There is accumulating evidence suggesting that transcriptional activation of heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation as well as the 32-kDa heat shock protein, participates in the defense against oxidative tissue injuries. Ischemia followed by reperfusion of the rat kidney accompanies significant induction of HO-1 mRNA, protein and enzyme activity, which is in part mediated through a rapid and transient increase in microsomal heme concentration. Inhibition of HO activity by tin mesoporphyrin results in a sustained and enhanced increase in microsomal heme content, and significantly exacerbates renal function. In contrast, SnCl2 treatment, which specifically induces HO-1 mRNA and protein in the proximal tubular epithelial cells, prevents the ischemia-reperfusion-mediated increase in microsomal heme concentration, and ameliorates the ischemic renal injury. In addition to these findings, recent evidence on the role of HO-1 in the kidney pathophysiology is summarized, with a particular emphasis on its protective role in the ischemic acute renal failure.
AuthorsReiko Akagi, Toru Takahashi, Shigeru Sassa (Affiliation: Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, Okayama-ken, Japan. akagirei at fhw.oka-pu.ac.jp)
JournalContributions to nephrology (Contrib Nephrol) Vol. 148 Pg. 70-85 ( 2005) ISSN: 0302-5144 [Print] Switzerland
PMID15912028 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • Membrane Proteins
  • HMOX1 protein, human
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
Topics
  • Animals
  • Cytoprotection (physiology)
  • Heme Oxygenase (Decyclizing) (metabolism)
  • Heme Oxygenase-1
  • Humans
  • Kidney Failure, Acute (metabolism, pathology)
  • Membrane Proteins

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