Differential regulation of human CYP4A genes by peroxisome proliferators and dexamethasone
Section snippets
Materials and methods
Cell culture and treatments. The generation of the HepG2 cell lines expressing the murine PPARα-E282G mutant or human PPARα (ha1 and ha2) as well as vector-transfected controls has been described [21]. Cells were seeded in Dulbecco’s modified Eagle’s medium (Invitrogen, Carlsbad, CA), supplemented with 10% fetal bovine serum (Summit, Ft. Collins, CO) and 500 μg/ml of Geneticin (G418) at a density that would reach 60% confluence after overnight culture. Cells were either untreated, treated with
Results
Kawashima et al. [24] characterized a human gene, currently annotated as CYP4A11 in the human genome project, that exhibits a coding sequence that is distinct but closely related to the reported human CYP4A11 cDNAs [22], [23]. The two sequences exhibit 95% identity leading the P450 Nomenclature Committee to confer a separate entry, CYP4A22, based on the low probability that the observed sequence differences would be seen in allelic genes. In order to test this hypothesis and to ascertain
Discussion
This study examines the potential for regulation of human CYP4A genes by PPARα and peroxisome proliferators. The increased expression of CYP4A genes in response to dietary fatty acids and peroxisome proliferators is regulated by PPARα in some species such as rabbits [13], rats [14], or mice [15], [16], but is not seen in guinea pigs [29], or nonhuman primates [30]. These species differences could reflect pharmacologic differences in receptor activation, differences in the expression of PPARα in
Acknowledgements
We thank Keith Griffin for critical reading of the manuscript. This work was supported by the United States Public Health Service Grant HD 04445.
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