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 language | English |
|---|---|
| Pages (from-to) | 27-32 |
| Number of pages | 6 |
| Journal | International Journal of Molecular Medicine |
| Volume | 26 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2010 |
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Keywords
- Apoptosis
- Inflammation
- Oxidative stress
- Resuscitation
ASJC Scopus subject areas
- Genetics
Cite this
Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock. / Arimori, Yutaka; Takahashi, Toru; Nishie, Hiroyuki; Inoue, Kazuyoshi; Shimizu, Hiroko; Omori, Emiko; Kawanishi, Susumu; Toda, Yuichiro; Morimatsu, Hiroshi; Morita, Kiyoshi.
In: International Journal of Molecular Medicine, Vol. 26, No. 1, 07.2010, p. 27-32.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock
AU - Arimori, Yutaka
AU - Takahashi, Toru
AU - Nishie, Hiroyuki
AU - Inoue, Kazuyoshi
AU - Shimizu, Hiroko
AU - Omori, Emiko
AU - Kawanishi, Susumu
AU - Toda, Yuichiro
AU - Morimatsu, Hiroshi
AU - Morita, Kiyoshi
PY - 2010/7
Y1 - 2010/7
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Inflammation
KW - Oxidative stress
KW - Resuscitation
UR - http://www.scopus.com/inward/record.url?scp=77954735305&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77954735305&partnerID=8YFLogxK
U2 - 10.3892/ijmm-00000430
DO - 10.3892/ijmm-00000430
M3 - Article
C2 - 20514418
AN - SCOPUS:77954735305
VL - 26
SP - 27
EP - 32
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
SN - 1107-3756
IS - 1
ER -