Centrilobular expression of ethanol-inducible cytochrome P-450 (IIE1) in rat liver.
Western blot analysis of digitonin eluates as well as immunohistochemical analysis revealed a 30-fold higher concentration of cytochrome P-450IIE1 in the centrilobular than in the periportal regions of the rat liver. Ethanol treatment caused a selective centrilobular induction of P-450IIE1, whereas phenobarbital induced P-450IIB1/2 in both liver lobule regions. The heterogeneous distribution pattern of P-450IIE1 was also observed in cells isolated from either region and correlated to the relative content of P-450IIE1 mRNA in the two cell types. The regiospecific expression and induction of P-450IIE1 may explain why several hepatotoxins, known to be metabolized by this isozyme, primarily damage the centrilobular region in the liver.
Ingelman-Sundberg
M
M
Department of Physiological Chemistry, Karolinska Institute, Stockholm, Sweden.
Johansson
I
I
Penttilä
K E
KE
Glaumann
H
H
Lindros
K O
KO
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D008099:Liver / Q000033:anatomy & histology / Q000201:enzymology*; D008297:Male; D051381:Rats
D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D000410:Alanine Transaminase; D005974:Glutamate-Ammonia Ligase