Cyclooxygenase-2 contributes to the selective induction of cell death by the endocannabinoid 2-arachidonoyl glycerol in hepatic stellate cells

185Scheme of proposed 2-arachidonoyl glycerol (2-AG) death signaling in hepatic stellate cells (HSCs). 2-AG binds to unknown structures in cholesterol rich lipid rafts. Primarily, 2-AG leads to intramitochondrial reactive oxygen species (ROS) production. Secondly, 2-AG is also metabolized to prostaglandin D2 glycerol ester (PGD2-GE) in the cytoplasm by cyclooxygenase-2 (COX-2). PGD2-GE and mitochondrial ROS induced by 2-AG lead to cytochrome C release from mitochondria to cause caspase-3-dependent apoptotic cell death in HSCs.