Ac IETD CHO somewhat suppressed the 6 OHDA induced caspase 9 activation. These results claim that 6 OHDA induced caspase 9 activation might be through caspase bosom of the Bid, 8 activation and cytochrome c release pathway. To examine the involvement of the p38 MAPK pathway in PC12 cells, the consequence of 6 OHDA on the phosphorylation of p38 was evaluated. 6 OHDA increased supplier Lenalidomide the level of p p38 in a manner. Moreover, the 6 OHDAinduced p38 phosphorylation was decreased by pCPT cAMP at-the same dose and chromatin condensation that was inhibited by time points. The accumulation of ROS has been reported to play a vital role in the 6 OHDA induced apoptosis. To acquire further insight into the system of the intracellular generation of ROS, we applied the superoxide mediated oxidation of hydroethidine to ethidium and immediately examined the rate of superoxide anion generation. As shown in Fig. 10A, the fluorescence intensity of ethidium was increased by the procedure with 6 OHDA in a time dependent manner. The increase in fluorescence intensity was observed from 2min after therapy with 50uM 6 OHDA. The fluorescence change was suppressed by tiron, Gene expression a of intracellular superoxide, but not by pCPTcAMP. More over, tiron also suppressed the 6 OHDA caused p38 phosphorylation, membrane depolarization and chromatin condensation. A higher concentration and longer pretreatment of tiron resulted in an even more noticeable inhibition of the membrane depolarization and chromatin condensation. These results suggest that the era of intracellular ROS, probably superoxide, is essential for your 6 OHDA induced apoptosis, and that 6 OHDA induced CsA insensitive mitochondrial membrane depolarization occurred through-the nonspecific membrane injury induced by ROS. The decrease in mitochondrial membrane potential was not restricted by pCPT cAMP and wasn’t apt to be included in the apoptosis machinery in this model. It has been noted that 6 OHDA triggers MPT in isolated brain mitochondria. In isolated rat liver mitochondria, we also noticed that 6 OHDA induces cytochrome c release through a mechanism, which confirmed mitochondrial swelling and membrane depolarization with a CsA delicate mechanism.