Orchiectomy attenuates post-ischemic oxidative stress and ischemia/reperfusion injury in mice - A role for manganese superoxide dismutase
- Authors
- Kim, Jinu; Kil, In Sup; Seok, Young Mi; Yang, Eun Sun; Kim, Dae Kyong; Lim, Dong Gun; Park, Jeen-Woo; Bonventre, Joseph V.; Park, Kwon Moo
- Issue Date
- 21-Jul-2006
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.281, no.29, pp 20349 - 20356
- Pages
- 8
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 281
- Number
- 29
- Start Page
- 20349
- End Page
- 20356
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24306
- DOI
- 10.1074/jbc.M512740200
- ISSN
- 0021-9258
1083-351X
- Abstract
- Males are much more susceptible to ischemia/reperfusion (I/R)-induced kidney injury when compared with females. Recently we reported that the presence of testosterone, rather than the absence of estrogen, plays a critical role in gender differences in kidney susceptibility to I/R injury in mice. Although reactive oxygen species and antioxidant defenses have been implicated in I/R injury, their roles remain to be defined. Here we report that the orchiectomized animal had significantly less lipid peroxidation and lower hydrogen peroxide levels in the kidney 4 and 24 h after 30 min of bilateral renal ischemia when compared with intact or dihydrotestosterone-treated orchiectomized males. The post-ischemic kidney expression and activity of manganese superoxide dismutase (MnSOD) in orchiectomized mice was much greater than in intact or dihydrotestosterone-administered orchiectomized mice. Four hours after 30 min of bilateral ischemia, superoxide formation was significantly lower in orchiectomized mice than in intact mice. In Madin-Darby canine kidney cells, a kidney epithelial cell line, 1 mM H2O2 decreased MnSOD activity, an effect that was potentiated by pretreatment with dihydrotestosterone. Orchiectomy prevented the post-ischemic decrease of catalase activity. Treatment of male mice with manganese(III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP), a SOD mimetic, reduced the post-ischemic increase of plasma creatinine, lipid peroxidation, and tissue hydrogen peroxide. These results suggest that orchiectomy accelerates the post-ischemic activation of MnSOD and reduces reactive oxygen species and lipid peroxidation, resulting in reduced kidney susceptibility to I/R injury.
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Collections - College of Pharmacy > School of Pharmacy > 1. Journal Articles
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