The inducing effect of S-nitrosoglutathione on the expression and activity of organic anion transporting polypeptide 1B1 (OATP1B1) in HepG2 cells.

Abstract

The effect of the nitric oxide donor S-nitrosoglutathione on the level and activity of organic anion transporting polypeptide 1B1 (OATP1B1), as well as the expression of the SLCO1B1 gene encoding the transporter protein, was investigated in HepG2 cells. The study has shown that treatment of cells with S-nitrosoglutathione for 3 h did not influence the content and activity of OATP1B1. Incubation with S-nitrosoglutathione (10-500 μM) for 24 h increased SLCO1B1 expression, the content of OATP1B1, and activity of the transporter protein. Induction of the OATP1B1 protein by the NO donor was suppressed by the soluble guanylate cyclase (sGC) inhibitor, 10 μM ODQ (1H-[1,2,4]oxadiazolo-[4,3-a]quinoxaline-1-OH). Thus, the study has shown that S-nitrosoglutathione, acting through the NO-sGC-cGMP signaling pathway, increased SLCO1B1 gene expression, accompanied by the increase in the transporter protein content and its activity in cells.