Araya Z, Sjöberg H, Wikvall K
Department of Pharmaceutical Biosciences, University of Uppsala, Sweden.
Biochem Biophys Res Commun. 1995 Nov 22;216(3):868-73. doi: 10.1006/bbrc.1995.2702.
It was recently reported that both cholesterol 7 alpha-hydroxylase CYP7 and sterol 27-hydroxylase CYP27 are subject to negative feedback control by bile acids in isolated rat hepatocytes and rat liver (Twisk et al., (1995) Biochem. J. 305, 505-511; Vlahcevic et al. XIII International Bile Acid Meeting, September 30-October 2, 1994, Abstract 17). In the present work a series of experiments was performed to study whether there is a coordinate regulation of CYP7 and CYP27 also in rabbit liver. Treatments of rabbits with cholic acid or cholestyramine resulted in marked suppression and induction, respectively, of CYP7 mRNA. In contrast, there were no significant effects on the CYP27 mRNA expression, amount of CYP27 protein or mitochondrial 27-hydroxylase activity. Thus, there is an apparent difference between rat and rabbit with respect to regulation of CYP27 by bile acids. It is concluded that, in rabbit, there is little or no coordinate regulation of CYP7 and CYP27 at a transcriptional level, and that CYP27 is not subject to a negative feedback control by bile acids neither at a transcriptional nor at a posttranscriptional level.
最近有报道称，胆固醇7α-羟化酶CYP7和甾醇27-羟化酶CYP27在分离的大鼠肝细胞和大鼠肝脏中均受到胆汁酸的负反馈控制（Twisk等人，（1995年）《生物化学杂志》305卷，505 - 511页；Vlahcevic等人，第十三届国际胆汁酸会议，1994年9月30日至10月2日，摘要17）。在本研究中，进行了一系列实验以研究在兔肝脏中CYP7和CYP27是否也存在协同调节。用胆酸或消胆胺处理兔子分别导致CYP7 mRNA明显受到抑制和诱导。相反，对CYP27 mRNA表达、CYP27蛋白量或线粒体27-羟化酶活性没有显著影响。因此，在胆汁酸对CYP27的调节方面，大鼠和兔子之间存在明显差异。得出的结论是，在兔中，在转录水平上CYP7和CYP27几乎没有或不存在协同调节，并且CYP27在转录水平和转录后水平均不受胆汁酸的负反馈控制。
