Taurine Decreases Cellular Cholesterol Level in HepG2 Cells Partly through Upregulating Calcineurin

Abstract Objective: Taurine exerts cholesterol-lowering effect through inducing CYP7A1 and promoting the biotransformation of cholesterol into bile acids in livers, but its molecular mechanism remains unclear. Taurine also suppresses the expression of MCIP1, a calcineurin inhibitory protein. Here we aimed to explore whether calcineurin involves in the cholesterol-lowering effect and upregulation of CYP7A1 by taurine. Methods: High cellular cholesterol conditions were obtained by incubating with 0.2mM cholesterol contained DMEM in HepG2 cells. FK506, a calcineurin inhibitor, was used to depress cellular calcineurin. CnAb -/- cells are the HepG2 cells of which calcineurin was knocked down. Taurine was cultured in wild type, high-cholesterol conditions, calcineurin inhibition or deficiency HepG2 cells respectively for 24h or 48h. The levels of intracellular total cholesterol were determined by an enzymatic method and the expressions of CYP7A1, calcineurin, MEK1/2, c-Jun/p-c-Jun and SHP-1 were detected by western blotting. Results: High cellular cholesterol conditions in HepG2 cells were established and resulted in increased CYP7A1 and calcineurin expression. Taurine exhibited the decreasing-cholesterol effects on HepG2 cells regardless of whether cells with high cholesterol conditions or inhibited / deleted intracellular calcineurin. However, the extent of decreasing cholesterol after calcineurin repression or deficiency was much less than that of controls. Taurine could induce the expression of CYP7A1 but this induction was abolished when the cellular calcineurin was inhibited or deleted. Taurine was able to suppress MEK1/2, p-c-Jun and SHP-1, which are several key molecules in one inhibitory pathway of CYP7A1 transcription, whereas this suppression on MEK1/2 but not p-c-Jun or SHP-1 was reversed after completely knocking down calcineurin. Conclusions: Calcineurin was found to be required partly in taurine-decreasing cholesterol effect through inhibiting MEK1/2 which resulted in CYP7A1 upregulation.