FIGURE 9.

Schematic presentation of proposed mechanism for GTPP-induced preconditioning against cell death induced by OGD/R. EGCG present in GTPP binds to 67LR and triggers cell signaling leading to activation of NADPH oxidase, which generates sublethal levels of ROS. ROS in turn activates PKCϵ by directly inducing its oxidative modification. In addition, ROS indirectly induces activation and membrane/mitochondrial translocation of PKCϵ through generation of phospholipid-hydrolysis products. Mitochondrial association of cell survival isoenzyme PKCϵ likely protects cells from cell death induced by OGD/R. Our previous studies have shown an activation of ERK by ROS in GTPP-treated cells as well as an activation of ERK by PKC in oxidant-treated cells triggering downstream nuclear events (20, 56). Based on these observations, we propose that GTPP induces expression of antioxidant enzymes that may precondition cells against OGD/R-induced cell death.