COX-2 관련 신경세포 사멸과정에서의 ROS의 역할

초록

Cyclooxygenase-2 (COX-2) has an oxygenase activity that catalyses PGG2 formation from arachidonic acid, and a peroxidase activity that reduces PGG2 to PGH2. However, the role of this dual enzyme activity of COX-2 in cell death is yet to be illucidated. In the current study, we examined the role of COX-2 in ROS-induced neuronal death in primary cortical culture. The pretreatment for more than 12 hours with IGF-I or LPS increased the neurotoxicity induced by 80 uM Zn+2 or 30 uM ferrous. The IGF-I or LPS-enhanced cell death was blocked by the COX-2 specific inhibitors, NS-398, and by the antioxidant, trolox. Cortical neurons pretreated with IGF-I and then Zn+2 showed enhanced reactive oxygen species (ROS) production, which was repressed by NS-398. Consistent with these pharmacological data, cortical neurons prepared from COX-2 deficient mice showed a reduction in LPS-enhanced neurotoxicity. These results suggest that COX-2 is an endogenous factor responsible for the IGF-I or LPS-induced potentiation of Zn2+ or ferrous toxicity in primary cortical cultures and the underlying mechanism involves COX-2-dependent ROS generation.