Reisdorph R, Lindahl R
Biochemistry and Molecular Biology Group, University of South Dakota School of Medicine, Vermillion 57069, USA.
Biochem Biophys Res Commun. 1998 Aug 28;249(3):709-12. doi: 10.1006/bbrc.1998.9216.
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.
3类醛脱氢酶基因(ALDH3)以组织特异性方式差异表达,在某些组织中组成性表达,而在其他组织中则通过芳烃受体/芳香烃受体核转运蛋白(Ah受体/ARNT)途径经外源性诱导表达。ARNT也参与低氧反应时的基因表达调控。它与低氧诱导因子1α(HIF-1α)二聚化,并增强低氧反应基因的表达。为了确定ARNT在低氧张力反应中是否对ALDH3的调节起作用,我们研究了1%氧气和低氧模拟物氯化钴对大鼠肝癌细胞和大鼠角膜上皮细胞中组成性和诱导性ALDH3表达的影响。低氧显著下调角膜上皮细胞中组成性ALDH3的表达。同样,低氧可显著降低H4-II-EC3细胞中芳烃诱导的ALDH3表达。相反,低氧对HTC细胞中组成性或芳烃诱导的ALDH3表达没有影响。我们的数据表明,低氧对组成性和诱导性ALDH3表达均产生细胞类型特异性影响。