High fluence low-power laser irradiation induces apoptosis via inactivation of Akt/GSK3β signaling pathway.

High fluence low-power laser irradiation (HF-LPLI) is a newly discovered stimulus through generating reactive oxygen species (ROS) to trigger cell apoptosis. Activation of glycogen synthase kinase 3β (GSK3β) is proved to be involved in intrinsic apoptotic pathways under various stimuli. However, whether the proapoptotic factor GSK3β participates in HF-LPLI-induced apoptosis has not been elucidated. Therefore, in the present study, we investigated the involvement of GSK3β in apoptosis under HF-LPLI treatment (120 J/cm2, 633 nm). We found that GSK3β activation could promote HF-LPLI-induced apoptosis, which could be prevented by lithium chloride (a selective inhibitor of GSK3β) exposure or by GSK3β-KD (a dominant-negative GSK3β) overexpression. We also found that the activation of GSK3β by HF-LPLI was due to the inactivation of protein kinase B (Akt), a widely reported and important upstream negative regulator of GSK3β, indicating the existence and inactivation of Akt/GSK3β signaling pathway. Moreover, the inactivation of Akt/GSK3β pathway depended on the fluence of HF-LPLI treatment. Furthermore, vitamin c, a ROS scavenger, completely prevented the inactivation of Akt/GSK3β pathway, indicating ROS generation was crucial for the inactivation. In addition, GSK3β promoted Bax activation by down-regulating Mcl-1 upon HF-LPLI treatment. Taken together, we have identified a new and important proapoptotic signaling pathway that is consisted of Akt/GSK3β inactivation for HF-LPLI stimulation. Our research will extend the knowledge into the biological mechanisms induced by LPLI.