Bile duct ligation impairs function and expression of breast cancer resistance protein in rat blood-retinal barrier mainly due to both the increased ammonia and bilirubin

-induced downregulation of BCRP protein. Confirming this in vivo, bilirubin and ammonium acetate recapitulated BCRP suppression via ROS-ERK1/2 and JNK pathways, respectively (n = 6 per group). In summary, BDL downregulated the expression and function of BCRP in rat retina, partly due to increases in levels of both ammonia and bilirubin. Ammonia impaired BCRP expression by inactivating the JNK pathway, while bilirubin suppressed BCRP expression by activating the ROS-ERK1/2 pathway. SIGNIFICANCE STATEMENT: Bile duct ligation-induced ammonia and bilirubin accumulation downregulated retinal breast cancer resistance protein (BCRP) expression and function. Ammonia impaired the expression of BCRP by inactivating the JNK pathway, while bilirubin suppressed BCRP expression through activating the ROS-ERK1/2 pathway.