Glutathione and bile acid synthesis. Effect of GSH content of HepG2 cells on the activity and mRNA levels of cholesterol 7 alpha-hydroxylase.

Cholesterol 7 alpha-hydroxylase (CH-7 alpha) activity in HepG2 cells depleted of glutathione (GSH) was reduced significantly (P < 0.05) compared to that in untreated controls. Northern blot analysis of poly A+ mRNA isolated from GSH-depleted and control HepG2 cells showed that there was a reduction in mRNA for CH-7 alpha in treated HepG2 cells that was commensurate with the reduction in CH-7 alpha activity. The fact that total RNA, rRNA, and mRNA for beta fibrinogen were unaltered by the depletion of GSH suggests that the change in steady-state CH-7 alpha mRNA content is specifically sensitive to GSH content. This observation represents the first demonstration, for human liver cells, that there is an interaction between GSH levels and the regulation of CH-7 alpha mRNA levels.