Fig. 6.

JNK/ERK inhibition reverses atRA-induced cholesterol accumulation. A, B: HepaRG cells were pretreated with SP600125 (SP; 50 µM) and/or PD98059 (PD; 50 µM) for 1 h and treated with atRA (1 µM) for 3 h. A: Protein levels were determined by Western blot analysis. B: mRNA levels were determined by qPCR (n = 3, mean ± SD). *** P < 0.001 versus atRA-treated group. C: HepaRG cells were pretreated with SP600125 (50 µM) and/or PD98059 (50 µM) for 1 h and treated with atRA (1 µM) for the time periods indicated. Total cholesterol levels were measured. Total cholesterol levels at the 72 h time point are presented (n = 3, mean ± SD). ** P < 0.01 versus atRA-treated group. D: A model depicting mechanisms for CYP7A1 repression by atRA is shown.