Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon.
Bergheim
Ina
I
Hohenheim University (140), Dep, Physiology of Nutrition, Stuttgart, Germany. ina.bergheim@freenet.de
Bode
Christiane
C
Parlesak
Alexandr
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000201:enzymology*; D044682:Colon, Ascending / Q000201:enzymology; D044683:Colon, Descending / Q000201:enzymology; D012809:Colon, Sigmoid / Q000201:enzymology; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis / Q000235:genetics / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics / Q000493:pharmacokinetics*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D008297:Male; D008875:Middle Aged
C400322:cytochrome P-450 CYP2C subfamily; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human