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Electronic Thesis and Dissertation Repository

2020

Bile acid transport

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Human Genetic Variation In Na+-Taurocholate Co-Transporting Polypeptide (Ntcp; Slc10a1) And Targeted Slc10a1 Disruption In Mice: Effects On Bile Acid And Rosuvastatin Transport, Laura E. Russell Sep 2020

Human Genetic Variation In Na+-Taurocholate Co-Transporting Polypeptide (Ntcp; Slc10a1) And Targeted Slc10a1 Disruption In Mice: Effects On Bile Acid And Rosuvastatin Transport, Laura E. Russell

Electronic Thesis and Dissertation Repository

Sodium-taurocholate co-transporting polypeptide (NTCP, SLC10A1) is the central bile acid uptake transporter on the basolateral membrane of hepatocytes. Pharmacological inhibition of NTCP is also being used to treat Hepatitis B and D, and NTCP transports a variety of drugs including cholesterol-lowering statins. Despite these crucial roles, limited knowledge exists regarding the effects of genetic variation in SLC10A1 on bile acid and rosuvastatin transport.

To address this, we characterized activity and protein expression of genetically variant SLC10A1 in vitro. Seven SLC10A1 genetic variants displayed robust reductions in NTCP-mediated transport of taurocholic acid and rosuvastatin and virtually absent NTCP protein …

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