Unlike our hope, CsA didn’t affect the 6 OHDA caused mitochondrial membrane depolarization and chromatin condensation. These results show that 6 OHDA caused apoptosis doesn’t occur through the mechanism of CMPT. Because we reported previously that a in Akt phosphorylation promotes apoptosis, and it’s been reported that the phosphorylation of Akt suppresses the activation of caspase 8 through r p38, the effect of 6 OHDA on the phosphorylation of Akt in PC12 cells was examined. 6 OHDA decreased the quantity of p Akt and the p Akt/Akt ratio. The cellular amount of p Akt was reported to increase as a result of cAMP through a phosphoinositide 3 kinase dependent pathway. Certainly, treatment with 8 adenosine 3?,5? cyclic monophosphate, that has been a permeable cAMP analog improved Akt phosphorylation. These results indicate that pCPT cAMP acts as an activator in PC12 cells. Somewhat, a substantial level of g Akt still remained, even after treatment with 6 OHDA. At the same time, the effect of pCPT cAMP to the 6 OHDA caused chromatin condensation was evaluated. pCPT cAMP suppressed the 6 OHDA induced chromatin condensation. Alternatively, the 6 OHDA induced chromatin condensation was enhanced by LY294002, which Plastid was an of PI3 kinase. These results suggest the PI3 kinase/Akt process is active in the 6 OHDA induced apoptosis of PC12 cells. As the cellular level of p Akt was increased and the 6 OHDAinduced chromatin condensation was suppressed by pCPTcAMP, the consequence of pCPT cAMP on the 6 OHDA induced caspase activation was examined. The service of caspase3, 8 and 9 by 6 OHDA was suppressed by pretreatment with 100 uM pCPT cAMP. The consequence of pCPT cAMP on the 6 OHDA induced mitochondrial membrane depolarization was examined with microscopic analysis by double staining with Hoechst33342 and JC 1, to analyze the process of apoptosis reduction by pCPT cAMP. Curiously, pCPT cAMP didn’t control the mitochondrial membrane depolarization even though that pCPT cAMP suppressed chromatin condensation in-the same cells. Flow cytometric analysis also confirmed that pCPT cAMP failed to control the PF299804 clinical trial mitochondrial depolarization induced by 6 OHDA. Cleavage of Bid by caspase 8 is shown to directly trigger the release of cytochrome c from mitochondria. Hence, we studied the influence of 6 OHDA on the cellular amount of cleaved Bid. Western blot analysis unmasked that Bid was present like a 22kDa protein in intact PC12 cells. 6 OHDA induced cleavage of Bid to create a 15kDa truncated Bid. That Bid cleavage was inhibited by the existence of 100uM pCPT cAMP. The effect of Ac IETD CHO, which was an of caspase 8 on the caspase 9 activation, was evaluated to ensure whether caspase 8 activation induces the caspase 9 activation, since 6 OHDA induces the cleavage of Bid and caspase 9 activation.