Post-translational reduction of cytochrome P450IIE by CCl4, its substrate.
The molecular mechanism of cytochrome P450IIE reduction by CCl4 was reexamined by measuring its enzyme activity, immunoreactive protein contents, and mRNA levels. Aniline hydroxylase and the amounts of immunoreactive P450IIE were rapidly decreased in a time-dependent manner after a single dose of CCl4. No changes were observed in the amounts of immunoreactive P450IIC and P450IA despite significant decreases decrease in their catalytic activities. However, the decreases in P450IIE enzyme activity and immunoreactive protein by CCl4 were not accompanied by a decline in its mRNA level. The data thus suggested a post-translational reduction of P450IIE by CCl4, probably due to specific destruction of the P450IIE protein by its own substrate rather than heme moiety.
Sohn
D H
DH
Laboratory of Metabolism and Molecular Biology, National Institute on Alcoholism, Rockville, MD 20852.
Yun
Y P
YP
Park
K S
KS
Veech
R L
RL
Song
B J
BJ
D000815:Aniline Hydroxylase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000494:pharmacology*; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics; D051381:Rats; D011919:Rats, Inbred Strains
D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride; D010088:Oxidoreductases; D000815:Aniline Hydroxylase; D019363:Cytochrome P-450 CYP1A1; D019362:Cytochrome P-450 CYP2B1