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

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)-alpha 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 tin-mesoporphyrin (0.5 micromol/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-alpha 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.

• Authors: Yutaka Arimori, Toru Takahashi, Hiroyuki Nishie, Kazuyoshi Inoue, Hiroko Shimizu, Emiko Omori, Susumu Kawanishi, Yuichiro Toda, Hiroshi Morimatsu, Kiyoshi Morita
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 26 Issue 1 Pg. 27-32 (Jul 2010) ISSN: 1791-244X [Electronic] Greece
• PMID: 20514418 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-bcl-2
• Tumor Necrosis Factor-alpha
• Nitric Oxide Synthase Type II
• Heme Oxygenase-1
• Caspase 3

Topics

• Animals
• Blotting, Northern
• Caspase 3 (metabolism)
• Gene Expression Profiling
• Heme Oxygenase-1 (genetics, metabolism)
• Immunohistochemistry
• Kidney (blood supply, metabolism, physiopathology)
• Male
• Nitric Oxide Synthase Type II (genetics)
• Proto-Oncogene Proteins c-bcl-2 (genetics)
• Rats
• Rats, Sprague-Dawley
• Resuscitation
• Shock, Hemorrhagic (physiopathology)
• Tumor Necrosis Factor-alpha (genetics)