3.2.1. Transport Proteins

Within the group of transporters, the bile salt export pump (BSEP, ABCB11), the Na+/taurochlorate cotransporting polypeptide (NTCP, SLC10A1) and the bile acyl-CoA synthetase (SLC27A5) interact very specifically with bile acids and are thus directly involved in bile acid and cholesterol homeostasis. For these transporters, a very significant concentration-dependent downregulation of gene expression was observed after treatment with the three most cytotoxic PAs (lasiocarpine, senecionine, and heliosupine). Even after exposure of HepaRG cells to echimidine and seneciphylline, a weaker but still significant downregulation was evident at 21 and 35 μM of the PAs. Less or non-cytotoxic PAs exhibited no or only weak effects on the expression of genes encoding the abovementioned transporters. A similar pattern was observed for the expression of the less bile-acid-specific transport proteins ABCB4, ABCC3, ABCC6, ABCG5, SLC22A7, SLC22A9, SLC51A, SLCO1B1 and SLCO2B1. For the genes encoding the transport proteins ABCB1, ABCC2, SLC51B, SLCO1B3, no substantial changes in gene expression were detected.
