IDENTIFICATION OF GLUCOCORTICOID-INDUCIBLE CYTOCHROMES-P-450 IN THE INTESTINAL-MUCOSA OF RATS AND MAN
IDENTIFICATION OF GLUCOCORTICOID-INDUCIBLE CYTOCHROMES-P-450 IN THE INTESTINAL-MUCOSA OF RATS AND MAN
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DOI：
10.1172/jci113156
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发表时间：
1987-10-01
影响因子：
15.9
通讯作者：
GUZELIAN, PS
中科院分区：
文献类型：
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作者：
WATKINS, PB;WRIGHTON, SA;GUZELIAN, PS
我们使用单克隆抗体和互补DNA（cDNA）的糖皮质激素诱导的肝细胞色素P-450在大鼠（P-450 p）和人（HLp）寻找相关的细胞色素在肠粘膜。在大鼠肠上皮细胞中，我们发现了两个地塞米松诱导的蛋白相关的类固醇诱导的肝crytochromes P-450。肠上皮细胞中这些蛋白的诱导与P-450 p相关的信使RNA和红霉素脱甲基酶的量增加有关，P-450 p和HLp的活性具有高度特征。对人空肠肠上皮细胞的类似研究揭示了一种微粒体蛋白，在免疫印迹上与HLp难以区分，并且大量RNA与HLp cDNA杂交。在人肠上皮细胞中，HLp相关细胞色素的特定浓度（以免疫化学方法或红霉素脱甲基酶活性测定）与人肝脏中发现的浓度相似，可以解释检测到的所有CO结合血红素蛋白。我们的结论是，肠粘膜含有突出的形式（S）P-450类似于肝细胞色素P-450 p的结构，功能和一些监管特点。
We used monoclonal antibodies and complementary DNAs (cDNAs) to glucocorticoid-inducible liver cytochromes P-450 in rats (P-450p) and in man (HLp) to search for related cytochromes in intestinal mucosa. In rat enterocytes, we found two dexamethasone-inducible proteins related to the steroid-inducible liver crytochromes P-450. Induction of these proteins in enterocytes was associated with increases in the amount of a P-450p-related messenger RNA and of erthromycin demethylase, an activity highly characteristic of P-450p and HLp. Similar studies on human jejunal enterocytes revealed a microsomal protein indistinguishable from HLp on immunoblots and an abundance of RNA hybridizing with HLp cDNA. In human enterocytes the specific concentration of the HLp-related cytochrome (measured immunochemically or as erythromycin demethylase activity) was similar to that found in human liver and could account for all of the CO-binding hemoprotein detected. We conclude that intestinal mucosa contains prominent forms(s) P-450 similar to liver cytochrome P-450p in their structure, function, and some regulatory characteristics.