Protein Abundance of Drug Transporters in Human Hepatitis C Livers
Autor: | Marek Droździk, Joanna Lapczuk-Romanska, Christoph Wenzel, Łukasz Skalski, Sylwia Szeląg-Pieniek, Mariola Post, Marta Syczewska, Mateusz Kurzawski, Stefan Oswald |
---|---|
Rok vydání: | 2022 |
Předmět: |
Organic Chemistry
Membrane Transport Proteins Organic Anion Transporters Hepacivirus General Medicine Hepatitis C Catalysis Neoplasm Proteins Computer Science Applications Inorganic Chemistry Liver hepatitis C liver cirrhosis Child–Pugh score drug transporter protein quantification real-time PCR liquid chromatography-mass spectrometry Tandem Mass Spectrometry ATP Binding Cassette Transporter Subfamily G Member 2 Humans Multidrug Resistance-Associated Proteins Physical and Theoretical Chemistry Molecular Biology Spectroscopy Chromatography Liquid |
Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7947 |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms23147947 |
Popis: | Transmembrane drug transport in hepatocytes is one of the major determinants of drug pharmacokinetics. In the present study, ABC transporters (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, and BSEP) and SLC transporters (MCT1, NTCP, OAT2, OATP1B1, OATP1B3, OATP2B1, OCT1, and OCT3) were quantified for protein abundance (LC-MS/MS) and mRNA levels (qRT-PCR) in hepatitis C virus (HCV)-infected liver samples from the Child–Pugh class A (n = 30), B (n = 21), and C (n = 7) patients. Protein levels of BSEP, MRP3, MCT1, OAT2, OATP1B3, and OCT3 were not significantly affected by HCV infection. P-gp, MRP1, BCRP, and OATP1B3 protein abundances were upregulated, whereas those of MRP2, MRP4, NTCP, OATP2B1, and OCT1 were downregulated in all HCV samples. The observed changes started to be seen in the Child–Pugh class A livers, i.e., upregulation of P-gp and MRP1 and downregulation of MRP2, MRP4, BCRP, and OATP1B3. In the case of NTCP, OATP2B1, and OCT1, a decrease in the protein levels was observed in the class B livers. In the class C livers, no other changes were noted than those in the class A and B patients. The results of the study demonstrate that drug transporter protein abundances are affected by the functional state of the liver in hepatitis C patients. |
Databáze: | OpenAIRE |
Externí odkaz: | |
Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |