Figure 6.

Chronic disturbance of ER calcium homeostasis induces PARP cleavage, diminishes inhibitory phosphorylation of the pro-apoptotic BAD protein and of the multifunctional GSK3b kinase, and impairs ERK and STAT3 signalling to promote genotoxicity and apoptosis. Liraglutide rescues PARP cleavage and activation of STAT3 and p53 kinases. It additionally induces Akt phosphorylation that relieves BAD and GSK3b activity to promote cell survival in the neuroblastoma SH-SY5Y cell line upon persistent ER stress. Twenty-four hours post seeding, SH-SY5Y cells were serum starved for 8 h and treated with 0 or 100 nM of thapsigargin for 16 h, in the presence or absence of 100 nM Liraglutide. Cells were harvested, and Bcl-2 phosphorylation [(a)] and BID expression [(b)] were determined by western blotting. β-Actin was used as the loading control to all western blot analyses. Each bar represents mean ± SEM from four independent experiments. Data is expressed as fold change to the control (CNTRL; unstressed/untreated conditions). Data was analysed by one- and two-way ANOVA, followed by post hoc Bonferroni’s multiple comparison t-test (^* p ≤ 0.05, ^** p ≤ 0.01 & ^*** p ≤ 0.001 compared to CNTRL; ^# p ≤ 0.05 & ^## p ≤ 0.01 compared to the corresponding thapsigargin-treated cells).