Evidence for elevation of cytochrome P4502E1 (alcohol-inducible form) mRNA levels in rat kidney following pyridine administration.
The effects of pyridine on renal cytochrome P4502E1 (CYP2E1) expression in rat have been examined by immunoblot and Northern blot analyses. Immunoblot analyses revealed that 2E1 protein levels were elevated from 1.4- to 4.6-fold following pyridine administration in a dose- and time-dependent manner. Northern blot analyses revealed that renal 2E1 poly(A)+ RNA levels increased from 1.4- to 3.8-fold following pyridine treatment and that these increases in 2E1 mRNA paralleled the dose- and time-dependent increases in 2E1 protein content. In contrast, hepatic 2E1 poly(A)+ RNA levels failed to increase following these same dosing regimens, suggesting that metabolic alterations, such as those associated with starvation, were not etiologic factors in renal 2E1 induction. These results show that pyridine induced CYP2E1 in kidney and that elevation of renal 2E1 protein levels accompanying pyridine administration occurred at least partly as a consequence of increased 2E1 poly(A)+ RNA levels. The results of this research reveal that regulatory mechanisms governing CYP2E1 expression may differ in hepatic and renal tissues.
Kim
H
H
Institute of Chemical Toxicology, Wayne State University, Detroit, MI 48201.
Kim
S G
SG
Lee
M Y
MY
Novak
R F
RF
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D010089:Oxidoreductases, N-Demethylating / Q000096:biosynthesis / Q000235:genetics* / Q000302:isolation & purification; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D011725:Pyridines / Q000494:pharmacology*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D015345:Oligonucleotide Probes; D011725:Pyridines; D012333:RNA, Messenger; D011061:Poly A; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D010089:Oxidoreductases, N-Demethylating; C023666:pyridine