LPLI inhibits apoptosis upstream of Bax translocation via a GSK-3beta-inactivation mechanism.

Low-power laser irradiation (LPLI), a non-damage physical therapy, which has been used clinically for decades of years, is shown to promote cell proliferation and prevent apoptosis. However, the underlying mechanisms that LPLI prevents cell apoptosis remain undefined. In this study, based on real-time single-cell analysis, we demonstrated for the first time that LPLI inhibits staurosporine (STS)-induced cell apoptosis by inactivating the GSK-3beta/Bax pathway. LPLI could inhibit the activation of GSK-3beta, Bax, and caspase-3 induced by STS. In the searching for the mechanism, we found that, LPLI can activate Akt, which was consistence with our former research, even in the presence of STS. In this anti-apoptotic process, the interaction between Akt and GSK-3beta increased gradually, indicating Akt interacts with and inactivates GSK-3beta directly. Conversely, LPLI decreased the interaction between GSK-3beta and Bax, with the suppression of Bax translocation to mitochondria, suggesting LPLI inhibits Bax translocation through inactivating GSK-3beta. These results were further confirmed by the experiments of co-immunoprecipitation. Wortmannin, an inhibitor of phosphatidylinositol 3'-OH kinase (PI3K), potently suppressed the activation of Akt and subsequent anti-apoptotic processes induced by LPLI. Taken together, we conclude that LPLI protects against STS-induced apoptosis upstream of Bax translocation via the PI3K/Akt/GSK-3beta pathway. These findings raise the possibility of LPLI as a promising therapy for neuron-degeneration disease induced by GSK-3beta.