Mouse P450RAI (CYP26) expression and retinoic acid-inducible retinoic acid metabolism in F9 cells are regulated by retinoic acid receptor γ and retinoid X receptor α
Mouse P450RAI (CYP26) expression and retinoic acid-inducible retinoic acid metabolism in F9 cells are regulated by retinoic acid receptor γ and retinoid X receptor α
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DOI：
10.1074/jbc.273.4.2409
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发表时间：
1998-01-23
影响因子：
4.8
通讯作者：
Petkovich, M
中科院分区：
文献类型：
--
作者：
Abu-Abed, SS;Beckett, BR;Petkovich, M
我们已经克隆了一个小鼠的cDNA同源物P450 RAI，细胞色素P450属于一个新的家庭（CYP 26），这是以前已经从斑马鱼和人类的cDNA分离，并发现编码视黄酸诱导的视黄酸羟化酶活性。氨基酸序列的跨物种保守性很高，特别是在小鼠和人的酶之间，其保守性超过90%。与人类和斑马鱼的对应物一样，当转染到COS-1细胞中时，小鼠P450 RAI cDNA催化视黄酸代谢为4-OH-视黄酸、4-氧代-视黄酸、18-OH-视黄酸和未鉴定的水溶性代谢物。先前已在F9小鼠胚胎癌细胞和缺乏类维生素A受体的某些衍生物中观察到视黄酸诱导的视黄酸代谢。我们感兴趣的是确定P450 RAI是否可以负责在F9细胞中的视黄酸代谢，并在研究的影响，视黄酸受体消融对P450 RAI的表达。在野生型F9细胞和缺乏RAR γ、RAR α和/或RXR α的衍生物中，我们观察到视黄酸代谢活性水平与视黄酸诱导的P450 RAI mRNA之间存在直接关系。这些实验以及其他使用合成受体亚型特异性类维生素A的实验表明，RAR γ和RXR α受体介导视黄酸对P450 RAI基因表达的影响。
We have cloned a mouse cDNA homolog of P450RAI, a cytochrome P450 belonging to a new family (CYP26), which has previously been isolated from zebrafish and human cDNAs and found to encode a retinoic acid-inducible retinoic acid hydroxylase activity. The cross-species conservation of the amino acid sequence is high, particularly between the mouse and the human enzymes, in which it is over 90%. Like its human and zibrafish counterparts, the mouse P450RAI cDNA catalyzes metabolism of retinoic acid into 4-OH-retinoic acid, 4-oxo-retinoic acid, 18-OH-retinoic acid, and unidentified water-soluble metabolites when transfected into COS-1 cells. Retinoic acid-inducible retinoic acid metabolism has previously been observed in F9 murine embryonal carcinoma cells and some derivatives lacking retinoid receptors. We were interested in determining whether P450RAI could be responsible for retinoic acid metabolism in F9 cells and in studying the effect of retinoid receptor ablation on P450RAI expression. In wild-type F9 cells and derivatives lacking RAR gamma, RAR alpha, and/or RXR alpha, we observed a direct relationship between the level of retinoic acid metabolic activity and retinoic acid-induced P450RAI mRNA. These experiments, as well as others using synthetic receptor subtype-specific retinoids, suggest that the RAR gamma and RXR alpha receptors mediate the effects of retinoic acid on the expression of the P450RAI gene.