Bergheim Ina, Bode Christiane, Parlesak Alexandr
Hohenheim University (140), Dep, Physiology of Nutrition, Stuttgart, Germany.
BMC Clin Pharmacol. 2005 Oct 27;5:4. doi: 10.1186/1472-6904-5-4.
Despite the fact that the alimentary tract is part of the body's first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon.
Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot methods.
Extensive interindividual variability was found for the expression of most of the genes. However, expression of CYP2C mRNA levels were significantly higher in the ascending colon than in the sigmoid colon. In contrast, mRNA levels of CYP2E1 and CYP3A5 were significantly lower in the ascending colon in comparison to the descending and sigmoid colon. In sigmoid colon protein levels of CYP2C8 were significantly higher by ~73% than in the descending colon. In contrast, protein concentration of CYP2E1 was significantly lower by ~81% in the sigmoid colon in comparison to the descending colon.
The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon.
尽管消化道是人体抵御经口摄入外源性物质的第一道防线的一部分，但关于细胞色素P450（CYP）酶在人结肠中的分布和表达却知之甚少。因此，我们测定了从升结肠、降结肠和乙状结肠获取的人结肠黏膜活检组织中四种代表性CYP（CYP2C8、CYP2E1、CYP3A4和CYP3A5）的表达和蛋白水平。
采用逆转录聚合酶链反应（RT-PCR）测定结肠黏膜中CYP2C、CYP2E1、CYP3A4和CYP3A5 mRNA的表达。使用蛋白质印迹法测定CYPs的蛋白浓度。
发现大多数基因的表达存在广泛的个体间差异。然而，CYP2C mRNA水平在升结肠中的表达明显高于乙状结肠。相反，与降结肠和乙状结肠相比，CYP2E1和CYP3A5的mRNA水平在升结肠中明显较低。在乙状结肠中，CYP2C8的蛋白水平比降结肠显著高约73%。相反，与降结肠相比，CYP2E1的蛋白浓度在乙状结肠中显著低约81%。
目前的数据表明，CYP2C、CYP2E1和CYP3A5的表达在结肠的不同部位有所不同。
