title: Effects of Trichostatin A on drug uptake transporters in primary rat hepatocyte cultures.
abstract: The present study was set up to investigate the effects of Trichostatin A (TSA), a prototypical epigenetic modifier, on the expression and activity of hepatic drug uptake transporters in primary cultured rat hepatocytes. To this end, the expression of the sinusoidal transporters sodium-dependent taurocholate cotransporting polypeptide (Ntcp) and organic anion transporting polypeptide 4 (Oatp4) was monitored by real-time quantitative reverse transcriptase polymerase chain reaction analysis and immunoblotting. The activity of the uptake transporters was analyzed using radiolabeled substrates and chemical inhibitors. Downregulation of the expression and activity of Oatp4 and Ntcp was observed as a function of the cultivation time and could not be counteracted by TSA. In conclusion, the epigenetic modifier TSA does not seem to exert a positive effect on the expression and activity of the investigated uptake transporters in primary rat hepatocyte cultures.
authors.affiliation: In Vitro Toxicology and Dermato-cosmetology research group, Center for Pharmaceutical Research, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel.
authors.forename: Eva
authors.initials: E
authors.lastname: Ramboer
authors.affiliation: In Vitro Toxicology and Dermato-cosmetology research group, Center for Pharmaceutical Research, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel.
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
authors.affiliation: In Vitro Toxicology and Dermato-cosmetology research group, Center for Pharmaceutical Research, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel.
authors.forename: Tamara
authors.initials: T
authors.lastname: Vanhaecke
authors.affiliation: In Vitro Toxicology and Dermato-cosmetology research group, Center for Pharmaceutical Research, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
keywords: Trichostatin A; drug transporters; epigenetics; primary hepatocyte culture