Zone-specific inducibility of cytochrome P450 2B1/2 is retained in isolated perivenous hepatocytes.
The expression and induction of the cytochrome P450 2B1/2 isoenzyme is heterogeneous, exhibiting a regional pattern in the intact liver and a varied response to phenobarbital in isolated cultured hepatocytes. We report that P450 2B1/2 immunostaining of hepatocytes isolated from the perivenous liver region and cultured in the presence of phenobarbital is much stronger than that of cells identically treated but isolated from the periportal region. P450 2B1 mRNA, quantified by a sensitive and specific RNAase protection assay, is also preferentially induced in perivenous hepatocytes, demonstrating that the difference in induced expression is at the pretranslational level. Our results suggest that perivenous and periportal hepatocytes are differentially imprinted to retain regiospecific factors governing their inducibility after isolation.
Bars
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RG
Biochemical Toxicology Section, I.C.I. Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, U.K.
Bell
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DR
Elcombe
C R
CR
Oinonen
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T
Jalava
T
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Lindros
K O
KO
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000098:blood supply / Q000166:cytology / Q000201:enzymology*; D008297:Male; D003012:Microbial Collagenase / Q000494:pharmacology; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014680:Veins
D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D003012:Microbial Collagenase; D010634:Phenobarbital