Negative regulation of the murine cytosolic aldehyde dehydrogenase-3 (Aldh-3c) gene by functional CYP1A1 and CYP1A2 proteins.
Negative regulation of the murine cytosolic aldehyde dehydrogenase-3 (Aldh-3c) gene by functional CYP1A1 and CYP1A2 proteins.
复制标题
功能性 CYP1A1 和 CYP1A2 蛋白对小鼠胞质醛脱氢酶 3 (Aldh-3c) 基因的负调控。
DOI：
10.1016/s0006-291x(05)81508-6
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发表时间：
1992
影响因子：
3.1
通讯作者：
Nebert,DW
中科院分区：
文献类型：
--
作者：
Vasiliou,V;Puga,A;Nebert,DW
我们已经研究了相应的酶活性和mRNA水平的醛脱氢酶-3基因编码的胞质（ALDH 3c）和微粒体（ALDH 3 m）的形式。在小鼠肝癌Hepa-1c 1c 7细胞培养物中，苯并[a]芘和2，3，7，8-四氯二苯并-对-二恶英（TCDD）可诱导ALDH 3c和ALDH 3 m酶活性，而在完整小鼠肝脏中的活性可忽略不计。ALDH 3c的组成型mRNA水平几乎不存在，而ALDH 3 m的那些是大量的;使用Hepa-1突变株系，我们表明，ALDH 3c和ALDH 3 m都是TCDD诱导的Ah受体依赖性机制。在缺乏功能性CYP 1A 1酶的未处理突变体细胞中，ALDH 3c的基础mRNA水平显著升高，但ALDH 3 m的基础mRNA水平没有显著升高;通过将功能性鼠CYP 1A 1或人CYP 1A 2酶引入这些突变体细胞中，可以恢复低ALDH 3c基础mRNA水平。这些数据表明，TCDD的诱导过程是不同的CYP 1A 1/CYP 1A 2代谢依赖性抑制组成型基因的表达，我们建议，后者的属性分类theAldh-3c基因，但不是theAldh-3 m基因，作为一个成员的鼠[Ah]电池。
We have examined enzyme activities and mRNA levels corresponding to aldehyde dehydrogenase-3 genes encoding cytosolic (ALDH3c) and microsomal (ALDH3m) forms. In contrast to negligible activities in the intact mouse liver, both ALDH3c and ALDH3m enzyme activities are inducible by benzo[a]pyrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) in mouse hepatoma Hepa-1c1c7 cell cultures. Constitutive mRNA levels of ALDH3c are virtually absent, whereas those of ALDH3m are substantial; using Hepa-1 mutant lines, we show that both ALDH3c and ALDH3m are TCDD-inducible by an Ah receptor-dependent mechanism. Basal mRNA levels of ALDH3c, but not those of ALDH3m, are strikingly elevated in untreated mutant cells lacking a functional CYP1A1 enzyme; low ALDH3c basal mRNA levels can be restored by introduction of a functional murine CYP1A1 or human CYP1A2 enzyme into these mutant cells. These data suggest that the TCDD induction process is distinct from the CYP1A1/CYP1A2 metabolism-dependent repression of constitutive gene expression; we suggest that this latter property classifies theAldh-3cgene, but not theAldh-3mgene, as a member of the murine [Ah] battery.