MESSENGER-RNA LEVELS OF THE HYPOXIA INDUCIBLE FACTOR (HIF-1) AND DNA-REPAIR GENES IN PERINATAL ASPHYXIA OF THE RAT

Hypoxia inducible factor 1 (HIF-1) is a transcription factor which is expressed, when mammalian cells are subjected to hypoxia, activating t he transcription of genes encoding proteins thought important for main taining 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 asp hyctic period. To rule out influences by the redox status we also dete rmined antioxidant enzyme mRNA levels for superoxide dismutase, catala se, glutathion peroxidase and performed electron spin resonance studie s. To study the link to protein phosphorylation as previously proposed , we evaluated mRNA levels for protein kinase C. As DNA breaks were re ported to occur in PA, we determined mRNA levels of two genes represen ting 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 asphycti c periods either and electron spin resonance failed to detect the pres ence of the hydroxyl radical. PKC significantly decreased with the len gth of the asphyctic period. ERCC2 and XRCC1 mRNAs were inducible duri ng the acute phase of asphyxia indicating early repair phenomena. HIF- 1 may not be relevant for periods of PA upto 20 minutes, the maximal s urvival time in our model. Neonatal factors may be responsible for tha t phenomenon although we cannot rule out that HIF-1 changes may occur at the protein level.