Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:mRNA levels of the hypoxia inducible factor (HIF-1) and DNA repair genes in perinatal asphyxia of the rat. 976 11

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays an important role in O(2) homeostasis. Numerous observations suggest that changes in reactive oxygen species affect HIF-1 alpha stabilization and HIF-1 alpha transcriptional activation in many cell types. The antioxidant enzyme manganese superoxide dismutase (MnSOD) modulates the cellular redox environment by converting superoxide (O(2)(*-)) to hydrogen peroxide and dioxygen. Previous results from our group have shown that overexpression of MnSOD in MCF-7 cells alters stabilization of HIF-1 alpha under hypoxic conditions; however, the underlying mechanism(s) is not known. Here, we tested the hypothesis that MnSOD regulates the expression of HIF-1 alpha by modulating the steady-state level of O(2)(*-). We found that decreasing MnSOD with small interfering RNA in MCF-7 cells resulted in (a) an associated increase in the hypoxic accumulation of HIF-1 alpha immunoreactive protein, (b) a significant increase in the levels of O(2)(*-) (P < 0.01), but (c) no significant change in the steady-state level of H(2)O(2). Removal of O(2)(*-) using spin traps (alpha-4-pyridyl-1-oxide-N-tert-butylnitrone and 5,5-dimethyl-1-pyrroline N-oxide) or the O(2)(*-) scavenger Tempol or an SOD mimic (AEOL10113) resulted in a decrease in HIF-1 alpha protein, consistent with the hypothesis that O(2)(*-) is an important molecular effector responsible for hypoxic stabilization of HIF-1 alpha. The evidence from both genetic and pharmaceutical manipulation is consistent with our hypothesis that O(2)(*-) can contribute to the stabilization of HIF-1 alpha.
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PMID:Manganese superoxide dismutase modulates hypoxia-inducible factor-1 alpha induction via superoxide. 1841 45