Figure 5.

Toxic bile acids (TBAs)-induced hepatocyte apoptosis. In cholestasis, bile secretion is impaired, resulting in elevated concentrations of TBAs within hepatocytes. TBAs can activate the ER stress pathway as well as generation of ROS. TBAs also sensitize hepatocytes to death receptors (Fas, TRAIL, and TNFα)-induced apoptosis. Particularly, TBAs trigger translocation of intracellular Fas bearing vesicles to the plasma membrane where they self-aggregate, activate Fas receptor complexes, and cause caspase apoptotic cascade. In addition, some bile acids also activate PKC-δ and/or JNK1/2 MAP kinase, both of which stimulate pro-apoptotic pathways