Regarding neuronal cell purpose, Akt has been proven to be necessary for the marketing of cell survival and preventing apoptosis through the phosphorylation of proapoptotic Bad and procaspase 9. Recently, it’s already been noted that p38 MAPK is induced in the 6 pan Chk inhibitor induced apoptosis. To acquire a better insight into the molecular mechanism of neuronal cell apoptosis induced by dopamine metabolites, we investigated the mechanism of 6 OHDA induced apoptosis of PC12 cells and its security promoted by antioxidants and cAMP. Within this report, we explained that 6 OHDA enhanced the intracellular superoxide production and induced caspase activation, Bid cleavage, mitochondrial membrane depolarization and chromatin condensation, which were independent of MPT in PC12 cells, and that cAMP suppressed the apoptosis through the recovery of the phospho Akt levels and the inhibition of p38 phosphorylation with no inhibition of superoxide era and mitochondrial membrane depolarization. 6 OHDA induced the chromatin condensation of PC12 cells, since it was seen by Hoechst staining. The chromatin condensation relied on 6 OHDA attention and the incubation time. At 50uM of 6 OHDA, clear chromatin condensation was noticed from 4 h and reached a maximum at 12h. The chromatin condensation was suppressed by the pretreatment with z VAD fmk, which was a Eumycetoma universal caspase inhibitor in a manner, which suggests the contribution of the caspase cascade in the apoptosis. Caspases are delivery proteases of apoptosis induced by various stimuli. Because z VAD fmk inhibited 6 OHDAinduced chromatin condensation, we examined the consequence of 6 OHDA on the actions of varied caspases using specific synthetic substrates for every molecule. 6 OHDA increased those activities of caspase 3, 8 and 9 in PC12 cells in a concentration dependent manner and time. These caspase activities increased at 2?4h after incubation with 6 OHDA and reached a maximum at 12h. Because 6 OHDA activated caspase 9, we suspected the mitochondrial membrane potential could be depolarized in 6 OHDA treated PC12 cells via an MPT procedure. Indeed, following the incubation with 6 OHDA, cells with large mitochondrial membrane potential decreased in a Afatinib EGFR inhibitor time and concentration dependent manner following 6 OHDA treatment. Flowcytometric analysis also confirmed the depolarization of the mitochondrial membrane potential. In this instance, we proved cytochrome c release from the mitochondria to cytosol. Since 6 OHDA caused mitochondrial membrane depolarization, the consequence of CsA, which was a specific inhibitor of MPT, to the chromatin condensation and membrane depolarization was examined to explain whether the apoptosis happened through MPT.