Detection of cytochrome P4503A (CYP3A) in human hepatic stellate cells.
In this study we have investigated the occurrence of cytochrome P450 isoforms and of related cytochrome P450 reductase in human hepatic stellate cells (hHSC), a type of cell having relevant roles in physiopathological conditions of the liver. By performing immunoblotting of hHSC microsomes and immunofluorescence analysis associated to confocal laser microscopy we detected only P450 enzymes belonging to the cytochrome P450 3A subfamily (CYP3A) as well as cytochrome P450 reductase. The presence of CYP3A was further indicated by detection of testosterone 6beta-hydroxylase activity in hHSC microsomes. Other important human P450 forms were either undetectable (CYP1A2, CYP2E1, CYP2C8/9/19 and CYP4A) or bearly detectable (CYP1A1) in hHSC. This is the first study showing existence of active cytochrome P450 isoforms in human HSC.
Parola
M
M
Department Experimental Medicine and Oncology, University of Torino, Italy. parola@medfarm.unito.it
Robino
G
G
Bordone
R
R
Leonarduzzi
G
G
Casini
A
A
Pinzani
M
M
Neve
E
E
Bellomo
G
G
Dianzani
M U
MU
Ingelman-Sundberg
M
M
Albano
E
E
D017667:Adipocytes / Q000378:metabolism*; D001189:Aryl Hydrocarbon Hydroxylases; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000032:analysis / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase; D010089:Oxidoreductases, N-Demethylating / Q000032:analysis / Q000378:metabolism*
D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase