FIG. 8.

Model for regulation of apoptosis by COX-2. Removal of NGF from differentiated PC12 cells elevates nNOS expression and activity, thereby leading to production of excess NO and superoxide, which contributes to cell death by producing peroxynitrite. Stimulation of COX-2 expression by agonists is concomitant with increased production of PGE₂. PGE₂ is released from the cells and can stimulate the prostaglandin (PG) receptors on PC12 cells, leading to an increase in DLC expression. Stimulation of DLC expression results in an increase in association of DLC with nNOS, causing inactivation of nNOS and thus reducing production of NO and superoxide. This may prevent PC12 cells apoptosis induced by NGF withdrawal.