mRNA 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 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.
University of Vienna, Dpt of Pediatrics, Austria.
M
M
Chiappe-Gutierrez
E
E
Kitzmueller
O
O
Labudova
G
G
Fuerst
H
H
Hoeger
R
R
Hardmeier
H
H
Nohl
L
L
Gille
B
B
Lubec
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002374:Catalase / Q000235:genetics; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D029721:Drosophila Proteins; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D005979:Glutathione Peroxidase / Q000235:genetics; D006863:Hydrogen-Ion Concentration; D017665:Hydroxyl Radical / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins / Q000096:biosynthesis*; D011247:Pregnancy; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000235:genetics; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; D051759:Xeroderma Pigmentosum Group D Protein
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D000076105:X-ray Repair Cross Complementing Protein 1; C000619372:Xrcc1 protein, rat; C078672:hay protein, Drosophila; D017665:Hydroxyl Radical; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D004265:DNA Helicases; D051759:Xeroderma Pigmentosum Group D Protein