IGF-1 protection against cerebellar granule neurons apoptosis induced by diphenylhydantoin through a PI3K/Akt dependent pathway / 中国药理学通报

ABSTRACT

Aim: To investigate the effects of insulin like growth factor1 (IGF-1) on apoptosis of cerebellar granule neurons (CGNs) induced by diphenylhydantoin (DPH) and its possible relationship with PI3K/Akt. Methods: Rat cerebellar granule neurons (CGNs), primarily cultured for 8 days, were co-incubated with 100 μmol·L-1 DPH and 1 μmol·L-1 IGF-1 for 48 h and then submitted to apoptotic analysis. CGNs, pretreated with 100 μmol·L-1 DPH and 1 μmol·L-1 IGF-1 for 48 h, were incubated with LY294002, a specific inhibitor of PI3K for 30 minutes, and then performed cell viability assays to explore the relationship of IGF-1 with PI3K/Akt pathway. Western blotting was employed to further study whether Akt was involved in the apoptotic effect of DPH and the protection of IGF-1. Results 1 μmol·L-1 IGF-1 demonstrated significant protective effects on apoptosis of CGNs treated with DPH, which could be abolished by LY294002, a specific inhibitor of PI3K/Akt pathway. IGF-1 also upregulated the activity of Akt in CGNs, which was markedly decreased by DPH. Conclusions: IGF-1 blocked the DPH-induced apoptosis of CGNs possibly through a PI3K/Akt dependent pathway.