Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock

Yutaka Arimori, Toru Takahashi, Hiroyuki Nishie, Kazuyoshi Inoue, Hiroko Shimizu, Emiko Omori, Susumu Kawanishi, Yuichiro Toda, Hiroshi Morimatsu, Kiyoshi Morita

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Hemorrhagic shock followed by resuscitation (HSR) causes oxidative stress, which results in multiple organ damage. The kidney is one of the target organs of HSR-mediated oxidative tissue injury. Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, is induced by oxidative stress; it protects against oxidative tissue injuries. The aim of the present study was to examine the role of renal HO-1 induction after HSR. Rats were subjected to hemorrhagic shock to achieve a mean arterial pressure of 30 mmHg for 60 min, followed by resuscitation with the shed blood. HSR resulted in a significant increase in functional HO-1 protein in the tubular epithelial cells of the kidney, whereas HSR resulted in only a slight increase in gene expression of tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS), and in protein expression of activated caspase-3 solely in renal cells where HO-1 expression was absent. HSR also resulted in a significant increase in Bcl-2 gene expression. Pretreatment of HSR animals with tinmesoporphyrin (0.5 μmol/kg), a specific competitive inhibitor of HO activity, resulted in a significant decrease in HO activity and exacerbated tissue inflammation and apoptotic cell death as judged by the marked increase in expression of TNF-α and iNOS, and in activated caspase-3-positive cells, and the significant reduction in Bcl-2 expression, respectively. These findings indicate that HO-1 induction is an adaptive response to HSR-induced oxidative stress and is essential for protecting tubular epithelial cells from oxidative damage through its anti-inflammatory and anti-apoptotic properties.

Original languageEnglish
Pages (from-to)27-32
Number of pages6
JournalInternational journal of molecular medicine
Volume26
Issue number1
DOIs
Publication statusPublished - Jul 2010

Keywords

  • Apoptosis
  • Inflammation
  • Oxidative stress
  • Resuscitation

ASJC Scopus subject areas

  • Genetics

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