Chiappe-Gutierrez M, Kitzmueller E, Labudova O, Fuerst G, Hoeger H, Hardmeier R, Nohl H, Gille L, Lubec B
University of Vienna, Dpt of Pediatrics, Austria.
Life Sci. 1998;63(13):1157-67. doi: 10.1016/s0024-3205(98)00377-4.
Hypoxia inducible factor 1 (HIF-1) is a transcription factor which is expressed, when mammalian cells are subjected to hypoxia, activating the transcription of genes encoding proteins thought important for maintaining oxygen hemostasis. The aim of the study was to evaluate HIF-1 mRNA levels in a non-invasive model of perinatal asphyxia (PA). Brain was taken for studies on HIF-1 alpha and beta 10 min following the asphyctic period. To rule out influences by the redox status we also determined antioxidant enzyme mRNA levels for superoxide dismutase, catalase, glutathion peroxidase and performed electron spin resonance studies. To study the link to protein phosphorylation as previously proposed, we evaluated mRNA levels for protein kinase C. As DNA breaks were reported to occur in PA, we determined mRNA levels of two genes representing DNA nucleotide excision repair, ERCC2 and ERCC3, and a DNA repair gene involved in the repair of oxidation mediated DNA damage, XRCC1. mRNAs for HIF-1 were not detectable following 5-20 minutes of asphyxia. The antioxidant enzymes did not show any changes during the asphyctic periods either and electron spin resonance failed to detect the presence of the hydroxyl radical. PKC significantly decreased with the length of the asphyctic period. ERCC2 and XRCC1 mRNAs were inducible during the acute phase of asphyxia indicating early repair phenomena. HIF-1 may not be relevant for periods of PA up to 20 minutes, the maximal survival time in our model. Neonatal factors may be responsible for that phenomenon although we cannot rule out that HIF-1 changes may occur at the protein level.
缺氧诱导因子1（HIF-1）是一种转录因子，当哺乳动物细胞处于缺氧状态时，它会表达，激活编码对维持氧稳态至关重要的蛋白质的基因转录。本研究的目的是评估围产期窒息（PA）非侵入性模型中HIF-1 mRNA水平。在窒息期后10分钟取出大脑，用于研究HIF-1α和β。为了排除氧化还原状态的影响，我们还测定了超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶的抗氧化酶mRNA水平，并进行了电子自旋共振研究。为了研究如先前提出的与蛋白质磷酸化的联系，我们评估了蛋白激酶C的mRNA水平。由于据报道PA中会发生DNA断裂，我们测定了代表DNA核苷酸切除修复的两个基因ERCC2和ERCC3以及参与氧化介导的DNA损伤修复的DNA修复基因XRCC1的mRNA水平。窒息5 - 20分钟后未检测到HIF-1的mRNA。抗氧化酶在窒息期间也未显示任何变化，电子自旋共振未能检测到羟基自由基的存在。PKC随着窒息时间的延长而显著降低。ERCC2和XRCC1 mRNA在窒息急性期可诱导，表明早期修复现象。在我们模型中最长存活时间20分钟内，HIF-1可能与PA期无关。尽管我们不能排除HIF-1在蛋白质水平可能发生变化，但新生儿因素可能是导致该现象的原因。
