title: Heme Oxygenase-1 is an Essential Cytoprotective Component in Oxidative Tissue Injury Induced by Hemorrhagic Shock.
abstract: Hemorrhagic shock causes oxidative stress that leads to tissue injuries in various organs including the lung, liver, kidney and intestine. Excess amounts of free heme released from destabilized hemoproteins under oxidative conditions might constitute a major threat because it can catalyze the formation of reactive oxygen species. Cells counteract this by rapidly inducing the rate-limiting enzyme in heme breakdown, heme oxygenase-1 (HO-1), which is a low-molecular-weight stress protein. The enzymatic HO-1 reaction removes heme. As such, endogenous HO-1 induction by hemorrhagic shock protects tissues from further degeneration by oxidant stimuli. In addition, prior pharmacological induction of HO-1 ameliorates oxidative tissue injuries induced by hemorrhagic shock. In contrast, the deletion of HO-1 expression, or the chemical inhibition of increased HO activity ablated the beneficial effect of HO-1 induction, and exacerbates tissue damage. Thus, HO-1 constitutes an essential cytoprotective component in hemorrhagic shock-induced oxidative tissue injures. This article reviews recent advances in understanding of the essential role of HO-1 in experimental models of hemorrhagic shock-induced oxidative tissue injuries with emphasis on the role of its induction in tissue defense.
authors.affiliation: Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama 700-8558, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shimizu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morimatsu
authors.forename: Kyoichiro
authors.initials: K
authors.lastname: Maeshima
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Inoue
authors.forename: Reiko
authors.initials: R
authors.lastname: Akagi
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katayama
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Morita