Protein Abundance of Drug Transporters in Human Hepatitis C Livers

• Published in: International journal of molecular sciences 2022-07, Vol.23 (14), p.7947
• Main Authors: Droździk, Marek, Lapczuk-Romanska, Joanna, Wenzel, Christoph, Skalski, Łukasz, Szeląg-Pieniek, Sylwia, Post, Mariola, Syczewska, Marta, Kurzawski, Mateusz, Oswald, Stefan
• Format: Article
• Language: English
• Subjects: ABC transporters; ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism; Bioavailability; Child–Pugh score; Cholangitis; Chromatography, Liquid - methods; cirrhosis; drug transporter; Drugs; Gene expression; Hepacivirus - metabolism; Hepatitis C; Hepatitis C - metabolism; Hepatocytes; Humans; Infections; Liver; Liver - metabolism; Liver diseases; Membrane Transport Proteins - genetics; Membrane Transport Proteins - metabolism; mRNA; Multidrug Resistance-Associated Proteins - genetics; Multidrug Resistance-Associated Proteins - metabolism; Neoplasm Proteins - metabolism; Oct-4 protein; Organic Anion Transporters - genetics; Organic Anion Transporters - metabolism; Pharmacokinetics; Polypeptides; protein quantification; Protein transport; Proteins; Tandem Mass Spectrometry - methods
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23147947

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 ( = 30), B ( = 21), and C ( = 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.