Chronic Hypoxia Impairs Cytochrome Oxidase Activity Via Oxidative Stress in Selected Fetal Guinea Pig Organs
Chronic Hypoxia Impairs Cytochrome Oxidase Activity Via Oxidative Stress in Selected Fetal Guinea Pig Organs
复制标题
DOI：
10.1177/1933719112453509
复制
发表时间：
2013-03-01
影响因子：
2.9
通讯作者：
Thompson, Loren P.
中科院分区：
文献类型：
--
作者：
Al-Hasan, Yazan M.;Evans, LaShauna C.;Thompson, Loren P.
我们假设慢性缺氧通过氧化应激破坏胎儿器官中的线粒体功能。妊娠豚鼠母猪暴露于常氧或缺氧（10.5%O-2，14天）的存在或不存在的抗氧化剂，N-乙酰半胱氨酸（NAC）。通过子宫切开术分娩近足月麻醉胎儿，收获胎儿肝脏、心脏、肺和前脑。我们量化了慢性缺氧对细胞色素氧化酶（CCO）活性和已知调节CCO活性的2个因子：丙二醛（MDA）和CCO亚基4（COX 4）的影响。缺氧增加了胎儿肝脏，心脏和肺中MDA的水平，相应地降低了CCO的活性，产前NAC阻止了这一变化。缺氧时，胎肝和胎肺中COX4的表达降低了CCO的活性，而胎心中COX4的表达无明显变化。缺氧降低脑COX4的表达，尽管对CCO活性没有影响。这项研究确定了在组织特异性氧化应激诱导胎儿缺氧损伤的一个重要的目标网站的cadion。
We hypothesized that chronic hypoxia disrupts mitochondrial function via oxidative stress in fetal organs. Pregnant guinea pig sows were exposed to either normoxia or hypoxia (10.5% O-2, 14 days) in the presence or absence of the antioxidant, N-acetylcysteine (NAC). Near-term anesthetized fetuses were delivered via hysterotomy, and fetal livers, hearts, lungs, and forebrains harvested. We quantified the effects of chronic hypoxia on cytochrome oxidase (CCO) activity and 2 factors known to regulate CCO activity: malondialdehyde (MDA) and CCO subunit 4 (COX4). Hypoxia increased the MDA levels in fetal liver, heart, and lung with a corresponding reduction in CCO activity, prevented by prenatal NAC. The COX4 expression paralleled CCO activity in fetal liver and lung, but was unaltered in fetal hearts due to hypoxia. Hypoxia reduced the brain COX4 expression despite having no effect on CCO activity. This study identifies the mitochondrion as an important target site in tissue-specific oxidative stress for the induction of fetal hypoxic injury.