Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P33527 (ABCC1)
 1,164 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic drug transporters are responsible for both hepatic uptake and the biliary excretion of drugs. Expression changes in hepatic drug transporter genes have been observed in various pathophysiological conditions. However, it has not been comprehensively investigated what factors substantially influence the mRNA levels of hepatic drug transporters. In this study, we quantified the mRNA expression of 17 drug transporters using noncancerous liver tissue samples and carried out stepwise multiple regression analysis to identify the factors affecting their expression from 18 clinical variables. For 17 drug transporters, the mRNA level of organic anion transporting polypeptide (OATP) 2B1 was highest, followed by that of organic cation transporter 1, organic anion transporter 2, OATP1B1, OATP1B3, multidrug resistance-associated protein (MRP) 6, and MRP3. Stepwise multiple regression analysis demonstrated MRP4 mRNA level to be predicted with the greatest accuracy among 17 drug transporters. Of clinical variables entered into the prediction model for MRP4, hepatitis C virus (HCV) infection and liver cirrhosis were crucial factors affecting MRP4 mRNA and protein levels. Furthermore, HCV-related cirrhosis influenced the mRNA levels of 8 drug transporters besides MRP4. These findings indicate that HCV-related cirrhosis is a crucial factor affecting the expression of hepatic drug transporters, especially MRP4.
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PMID:Hepatitis C virus-related cirrhosis is a major determinant of the expression levels of hepatic drug transporters. 2046 Aug 25

Human hepatoma cells may represent a valuable alternative to the use of human hepatocytes for studying hepatic drug transporters, which is now a regulatory issue during drug development. In the present work, we have characterized hepatic drug transporter expression, activity and regulation in human hepatoma HuH-7 cells, in order to determine the potential relevance of these cells for drug transport assays. HuH-7 cells displayed notable multidrug resistance-associated protein (MRP) activity, presumed to reflect expression of various hepatic MRPs, including MRP2. By contrast, they failed to display functional activities of the uptake transporters sodium taurocholate co-transporting polypeptide (NTCP), organic anion-transporting polypeptides (OATPs) and organic cation transporter 1 (OCT1), and of the canalicular transporters P-glycoprotein and breast cancer resistance protein (BCRP). Concomitantly, mRNA expressions of various sinusoidal and canalicular hepatic drug transporters were not detected (NTCP, OATP1B1, organic anion transporter 2 (OAT2), OCT1 and bile salt export pump) or were found to be lower (OATP1B3, OATP2B1, multidrug and toxin extrusion protein 1, BCRP and MRP3) in hepatoma HuH-7 cells than those found in human hepatocytes, whereas other transporters such as OAT7, MRP4 and MRP5 were up-regulated. HuH-7 cells additionally exhibited farnesoid X receptor (FXR)- and nuclear factor erythroid 2-related factor 2 (Nrf2)-related up-regulation of some transporters. Such data indicate that HuH-7 cells, although expressing rather poorly some main hepatic drug transporters, may be useful for investigating interactions of drugs with MRPs, notably MRP2, and for studying FXR- or Nrf2-mediated gene regulation.
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PMID:Drug Transporter Expression and Activity in Human Hepatoma HuH-7 Cells. 2803 31