Cytochrome P-450 mRNA expression in human liver and its relationship with enzyme activity.
CYP activity and protein contents have been measured in human liver using different techniques. In contrast, CYP mRNA data are scarce and the relationships between CYP mRNA contents and activities have not been established. These studies deserve further attention because mRNA determinations by RT-PCR require a very small amount of material (e.g., liver needle biopsy) and could provide important data regarding CYP expression regulation. In this study we measured in 12 human liver samples the mRNA contents of 10 CYPs by quantitative RT-PCR and the metabolic activities using specific substrates. mRNA contents and activities showed high correlation coefficients for CYP1A1, CYP1A2, CYP3A4, CYP2D6, and CYP2B6 (0.96, 0.94, 0.69, 0.61, and 0.52, respectively), but no significant correlations were found for CYP2C9, CYP2A6, and CYP2E1. The results suggest that the regulation of CYP1A1, CYP1A2, CYP3A4, CYP2D6, and CYP2B6 expression is essentially pretranslational and that their mRNA levels could allow a good estimate of their activity.
Rodríguez-Antona
C
C
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Valencia, Avenida Blasco Ibáñez 20, Valencia, E-46010, Spain.
Donato
M T
MT
Pareja
E
E
Gómez-Lechón
M J
MJ
Castell
J V
JV
D000328:Adult; D000368:Aged; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis
D007527:Isoenzymes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System