Hypoxia exerts cell-type-specific effects on expression of the class 3 aldehyde dehydrogenase gene.
The Class 3 aldehyde dehydrogenase gene (ALDH3) is expressed differentially in a tissue-specific manner, occurring constitutively in some tissues and in others as a result of xenobiotic induction via the Ah receptor/ARNT pathway. ARNT is also involved in regulating gene expression in response to hypoxia. It dimerizes with hypoxia-inducible factor 1 alpha (HIF-1 alpha) and enhances expression of hypoxia-responsive genes. To determine if ARNT plays a role in regulating ALDH3 in response to low oxygen tension, we studied the effects of 1% oxygen and the hypoxia mimic cobalt chloride on constitutive and inducible ALDH3 expression in rat hepatoma cells and rat corneal epithelial cells. Hypoxia sharply down-regulates constitutive ALDH3 expression in corneal epithelial cells. Likewise, aromatic hydrocarbon-induced ALDH3 expression in H4-II-EC3 cells is significantly reduced by hypoxia. In contrast, hypoxia has no effect on constitutive or aromatic hydrocarbon-inducible ALDH3 expression in HTC cells. Our data indicate that hypoxia exerts cell type-specific effects on both constitutive and induced ALDH3 expression.
Reisdorph
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Biochemistry and Molecular Biology Group, University of South Dakota School of Medicine, Vermillion 57069, USA.
Lindahl
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D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000818:Animals; D015687:Cell Hypoxia / Q000235:genetics*; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D019573:Epithelium, Corneal / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000235:genetics; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics; D008748:Methylcholanthrene / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; C030863:corneal protein 54, bovine; D003035:Cobalt; D008748:Methylcholanthrene; D007770:L-Lactate Dehydrogenase; D000444:Aldehyde Dehydrogenase; C018021:cobaltous chloride