Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria.
Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria.
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胎儿编程改变了绵羊心脏线粒体中活性氧的产生。
DOI：
10.1042/cs20080474
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发表时间：
2009
期刊：
影响因子：
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通讯作者：
Scholz,ThomasD
中科院分区：
文献类型：
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作者：
vonBergen,NicholasH;Koppenhafer,StaciaL;Spitz,DouglasR;Volk,KennethA;Patel,SonaliS;Roghair,RobertD;Lamb,FredS;Segar,JeffreyL;Scholz,ThomasD
暴露于不利的宫内环境被认为是日后发生心血管疾病的重要危险因素。虽然氧化应激被认为是胎儿编程表型的一种机制，但线粒体O2·−（超氧自由基）产生的作用尚未被探索。为了确定线粒体ROS（活性氧）的产生是否被子宫编程改变，妊娠母羊在妊娠27-28天（足月=145天）输注48小时地塞米松（地塞米松暴露，0.28 mg·kg-1体重·d-1）或盐水（对照）。完整的左心室线粒体和冻融线粒体膜进行了研究，从后代在4个月大。AmplexRed用于测量H2 O2产生。抗氧化酶Mn-SOD（锰超氧化物歧化酶），GPx（谷胱甘肽过氧化物酶）和过氧化氢酶的活性进行了测定。与对照组相比，地塞米松暴露动物的完整线粒体中复合物I H2 O2的产生显著增加。在线粒体膜中未观察到复合物I驱动的H2 O2产生的处理差异。程序化动物中复合物III的H2 O2产生没有发现一致的变化。尽管程序化动物完整线粒体中H2 O2的产生增加，但地塞米松暴露显着增加线粒体过氧化氢酶活性，而Mn-SOD和GPx活性没有变化。本研究的结果表明，尽管过氧化氢酶活性增加，但程序化线粒体释放H2 O2的速率增加。更多的线粒体H2 O2释放到细胞中可能在暴露于不利的宫内环境后成人疾病的发展中发挥作用。
Exposure to an adverse intrauterine environment is recognized as an important risk factor for the development of cardiovascular disease later in life. Although oxidative stress has been proposed as a mechanism for the fetal programming phenotype, the role of mitochondrial O2•−(superoxide radical) production has not been explored. To determine whether mitochondrial ROS (reactive oxygen species) production is altered byin uteroprogramming, pregnant ewes were given a 48-h dexamethasone (dexamethasone-exposed, 0.28 mg·kg−1of body weight·day−1) or saline (control) infusion at 27–28 days gestation (term=145 days). Intact left ventricular mitochondria and freeze-thaw mitochondrial membranes were studied from offspring at 4-months of age. AmplexRed was used to measure H2O2production. Activities of the antioxidant enzymes Mn-SOD (manganese superoxide dismutase), GPx (glutathione peroxidase) and catalase were measured. Compared with controls, a significant increase in Complex I H2O2production was found in intact mitochondria from dexamethasone-exposed animals. The treatment differences in Complex I-driven H2O2production were not seen in mitochondrial membranes. Consistent changes in H2O2production from Complex III in programmed animals were not found. Despite the increase in H2O2production in intact mitochondria from programmed animals, dexamethasone exposure significantly increased mitochondrial catalase activity, whereas Mn-SOD and GPx activities were unchanged. The results of the present study point to an increase in the rate of release of H2O2from programmed mitochondria despite an increase in catalase activity. Greater mitochondrial H2O2release into the cell may play a role in the development of adult disease following exposure to an adverse intrauterine environment.