Isolation and characterization of a new major intestinal CYP3A form, CYP3A62, in the rat.
Based on information of the nucleotide sequence obtained from rat genome clones, a new CYP3A (CYP3A62) cDNA was isolated from the cDNA library of a rat liver. The CYP3A62 cDNA was 1746 base pairs (bp) in length, which included 1491 bp of an open reading frame and 93 bp and 209 bp of the respective 5'- and 3'-noncoding regions. Amino acid sequence deduced from CYP3A62 cDNA shared the highest similarity with rat CYP3A9 (79.9%) among human and rat CYP3A forms previously reported. CYP3A62 mRNA and protein were consistently detected in small intestines as well as livers. CYP3A62 was a major form in small intestines of both sexes but was a female-predominant form in livers of adult rats. CYP3A62 in both tissues of male and female rats were clearly enhanced by the treatment with dexamethasone. These expression profiles resembled those of CYP3A9. Despite clear detection of CYP3A62, no detectable levels of CYP3A1 and CYP3A2 proteins, as well as those of mRNAs, were found in the intestinal tract. Therefore, CYP3A62 may play major roles together with CYP3A9 and CYP3A18 in endogenous or exogenous detoxification at the absorption site.
Matsubara
T
T
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8578, Japan.
Kim
H J
HJ
Miyata
M
M
Shimada
M
M
Nagata
K
K
Yamazoe
Y
Y
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000302:isolation & purification*; D001483:Base Sequence; D002384:Catalysis; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000302:isolation & purification*; D005260:Female; D007422:Intestines / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification; D008969:Molecular Sequence Data; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics / Q000302:isolation & purification*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism; D012689:Sequence Homology, Nucleic Acid
D008565:Membrane Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; C487405:Cyp3a62 protein, rat; C415842:Cyp3a9 protein, rat; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating