عنوان المقالة:Comparative analysis of the nuclear receptors CAR, PXR and PPAR in the regulation of hepatic energy homeostasis and xenobiotic metabolism
Nuclear receptors (NRs), most notably the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR), regulate the transcription of several drug metabolizing enzymes and transporters (DMET) and thus represent important regulators of drug metabolism in the liver. Accordingly, the ligand dependent activation of these NRs by drugs and other xenobiotics contributes to the intra- and inter-individual variability of the drug detoxifying system. CAR and PXR were further shown to regulate the transcription of key enzymes involved in lipid and glucose metabolism. The NR peroxisome proliferator-activated receptor alpha (PPAR), a key regulator of fatty acid catabolism and target of lipid lowering fibrates, was recently identified as a direct regulator of cytochrome P450 3A4 (CYP3A4) and also potentially of other DMET genes. In this respect, CAR, PXR and PPAR are determinants of an overlapping number of liver functions including drug metabolism and energy homeostasis and are therefore associated with adverse drug reactions as well as liver disease like steatosis. Until now there have been no comparative studies investigating the transcriptomes of CAR, PXR and PPAR in humans. Therefore, a major focus of this study was to assess the genome-wide transcriptional changes provoked by these NRs in primary human hepatocytes (PHHs). To investigate human liver-specific gene expression and its regulation PHHs represent the most suitable available in vitro cell system.
د محمد محمود محمد عبد الفتاح | DR MOHAMMAD MAHMOUD MOHAMMAD ADEL FATAH | 9780