Orchiectomy attenuates post-ischemic oxidative stress and ischemia/reperfusion injury in mice - A role for manganese superoxide dismutase
Orchiectomy attenuates post-ischemic oxidative stress and ischemia/reperfusion injury in mice - A role for manganese superoxide dismutase
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DOI：
10.1074/jbc.m512740200
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发表时间：
2006-07-21
影响因子：
4.8
通讯作者：
Park, Kwon Moo
中科院分区：
文献类型：
--
作者：
Kim, Jinu;Kil, In Sup;Park, Kwon Moo
与女性相比，男性更容易受到缺血/再灌注(I/R)所致的肾脏损伤。最近我们报道，睾丸激素的存在，而不是雌激素的缺乏，在小鼠肾脏对I/R损伤易感性的性别差异中起着关键作用。尽管活性氧和抗氧化剂防御与I/R损伤有关，但它们的作用仍有待明确。在此，我们报告了双侧肾缺血30分钟后，与正常或双氢睾酮治疗的雄性相比，切除睾丸的动物肾脏中的脂质过氧化作用和过氧化氢水平显著降低。去睾丸小鼠肾脏缺血后锰超氧化物歧化酶(MnSOD)的表达和活性明显高于正常小鼠和双氢睾丸酮注射小鼠。双侧脑缺血30min后4小时，去小鼠的超氧化物歧化显著低于正常小鼠。在肾上皮细胞系Madin-Darby犬肾细胞中，1 mM H_2O_2可降低MnSOD活性，这种作用可被双氢睾酮增强。切除可预防缺血后过氧化氢酶活性的下降。用锰(III)四(1-甲基-4-吡啶)卟啉(MnTMPyP)(一种超氧化物歧化酶的模拟物)处理雄性小鼠，可以减少缺血后血浆肌酐、脂质过氧化和组织过氧化氢的增加。这些结果表明，切除可加速缺血后MnSOD的激活，减少活性氧和脂质过氧化，从而降低肾脏对I/R损伤的易感性。
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.