Abstract
BackgroundDespite 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.MethodsExpression 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.ResultsExtensive 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.ConclusionThe current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon.
Highlights
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
The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon
Expression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in ascending, descending, and sigmoid colon The presence of a band of the correct size in agarose gels was regarded as evidence of gene expression
Summary
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. Despite the fact that it has been suggested that the absence of some of these microsomal enzymes in the colon may be involved in the comparably high incidence of carcinoma in this organ [4], information available on the expression of CYPs in the large intestine of humans is limited and some of the available data are contradictory. The main purpose of the present study was to evaluate the expression pattern, protein concentration, and distribution of four representative CYPs (CYP2C, CYP2E1, CYP3A4, and CYP3A5) in ascending, descending and sigmoid human colon mucosa of virtually healthy subjects.
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