The transcriptional activity and nuclear localization of FoxO3a is negatively regulated by AKT mediated phosphorylation. In line with this we discovered that IGF 1 avoided the potassium deprivation induced reduction in AKT exercise, FoxO3a dephosphorylation and attenuated Puma induction. Interestingly, we discovered that inhibition of Gemcitabine 122111-03-9 either JNK or GSK3b also inhibited FoxO3a dephosphorylation/activation. These effects were surprising given that GSK3b is activated downstream of AKT and that JNK signaling does not seem to affect AKT activity in this context. This means that JNK and GSK3b can control FoxO3a phosphorylation by an indirect mechanism or via an AKT independent mechanism possibly by regulating the action of the phosphatase involved with FoxO3a dephosphorylation. Though GSK3b and JNK were found to influence FoxO3a service we cannot rule out the likelihood that they may also manage other transcription factors involved in Puma induction. A candidate factor downstream of GSK3b is nuclear factor of activated T cells which has been shown to be phosphorylated by GSK3b resulting in its move from Retroperitoneal lymph node dissection the nucleus and promotion of success in CGNs. In this case NFAT may act as a repressor of Puma transcription that will be eliminated upon GSK3b activation. Equally, beta catenin may be working to reduce Puma induction until inactivated by GSK3b. Phosphorylation of beta catenin by GSK3b causes its translocation from the nucleus and targets it for degradation and inhibition of the phosphorylation event is connected with neuronal survival. Finally, there are lots of downstream targets of the JNK pathway which may manage Puma expression ALK inhibitor following JNK activation, these generally include c Jun, activating transcription factor 3 and activating transcription factor 2. A primary downstream goal of JNK, c Jun is found to be up-regulated in trophic factor deprived nerves and ectopic expression of dominant bad c Jun was found to protect against cell death. The JNK regulated transcription factors ATF2 and ATF3 may also be induced in a reaction to potassium deprivation and it’s been noted that knockdown or inhibition of these factors can protect neurons against apoptosis. It’s remarkable the Puma promoter contains putative AP1 binding sites which will be the known target sequence for all three of these transcription factors, suggesting a potential function for these factors in Puma induction. Interestingly, a current study implicated d Jun in the regulation of Puma term in fatty-acid induced apoptosis of hepatocytes, even though AP 1 binding site identified in this study doesn’t look like protected. It’s uncertain whether they play a role in Puma up-regulation within this context and is under investigation while these transcription factors have been implicated in neuronal apoptosis. In conclusion, we’ve delineated a key process involved in the regulation of apoptosis induced by potassium starvation in CGNs.