JNK and AKT/GSK3β signaling pathways converge to regulate periodontal ligament cell survival involving XIAP

Abstract Periodontal ligament cells (PDLCs) were incubated with H 2 O 2 and the levels of XIAP protein, protein kinase B (AKT), phosphorylated forms of AKT (pAKT), c-Jun N-terminal kinase (JNK), and glycogen synthase kinase-3β (GSK3β) were determined by western immunoblotting or immunocytochemistry. After overexpression and knockdown of XIAP, the AKT, pAKT, JNK and GSK3β levels were determined in PDLCs exposed to H 2 O 2 . We demonstrated that 72 h of 250 μM H 2 O 2 exposure resulted in an increase in apoptosis. Meanwhile, XIAP levels were decreased with 72 h of 250 μM H 2 O 2 exposure, while there were also a decrease of JNK2, AKT, pAKT, and GSK3β levels. Such reductions induced by 72 h of 250 μM H 2 O 2 treatment were partially recovered in PDLCs overexpressing XIAP. Interestingly, these reductions (except for pAKT) were mimicked by RNA interference of XIAP. These results suggest that, after 72 h of 250 μM H 2 O 2 exposure, Akt, JNK, and GSK3β intracellular kinase signaling pathways converge to regulate PDLC survival involving XIAP.