Differential Gene Regulation in Human Versus Rodent Hepatocytes by Peroxisome Proliferator-activated Receptor (PPAR) α
| Autor: | Diane R. Umbenhauer, Joel P. Berger, Gaochao Zhou, Shiying Chen, David E. Moller, Jeffrey W. Lawrence, John G. DeLuca, Ying Li |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Regulation of gene expression
chemistry.chemical_classification Messenger RNA medicine.medical_specialty Receptor expression Peroxisome Proliferation Peroxisome proliferator-activated receptor Cell Biology Transfection Biology Peroxisome Biochemistry Molecular biology Endocrinology chemistry Internal medicine medicine Receptor Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 276:31521-31527 |
| ISSN: | 0021-9258 |
| Popis: | We compared the ability of rat and human hepatocytes to respond to fenofibric acid and a novel potent phenylacetic acid peroxisome proliferator-activated receptor (PPAR) α agonist (compound 1). Fatty acyl-CoA oxidase (FACO) activity and mRNA were increased after treatment with either fenofibric acid or compound 1 in rat hepatocytes. In addition, apolipoprotein CIII mRNA was decreased by both fenofibric acid and compound 1 in rat hepatocytes. Both agonists decreased apolipoprotein CIII mRNA in human hepatocytes; however, very little change in FACO activity or mRNA was observed. Furthermore, other peroxisome proliferation (PP)-associated genes including peroxisomal 3-oxoacyl-CoA thiolase (THIO), peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (HD), peroxisomal membrane protein-70 (PMP-70) were not regulated by PPARα agonists in human hepatocytes. Moreover, other genes that are regulated by PPARα ligands in human hepatocytes such as mitochondrial HMG-CoA synthase and carnitine palmitoyl transferase-1 (CPT-1) were also regulated in HepG2 cells by PPARα agonists. Several stably transfected HepG2 cell lines were established that overexpressed human PPARα to levels between 6- and 26-fold over normal human hepatocytes. These PPARα-overexpressing cells had higher basal mRNA levels of mitochondrial HMG-CoA synthase and CPT-1; however, basal FACO mRNA levels and other PP-associated genes including THIO, HD, or PMP-70 mRNA were not substantially affected. In addition, FACO, THIO, HD, and PMP-70 mRNA levels did not increase in response to PPARα agonist treatment in the PPARα-overexpressing cells, although mitochondrial HMG-CoA synthase and CPT-1 mRNAs were both induced. These results suggest that other factors besides PPARα levels determine the species-specific response of human and rat hepatocytes to the induction of PP. |
| Databáze: | OpenAIRE |
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