White light emitting diode induces autophagy in hippocampal neuron cells through GSK-3-mediated GR and RORα pathways

Autophagy plays an important role in cell survival under diverse stress conditions. Here, we show that white LED light exposure for 24 h significantly activated autophagy-related genes and increased autophagosome formation in hippocampal neural cells (HT-22). Concurrently, the rhythmic pattern of clock-related gene expression was disrupted, which was associated with augmented expression of SIRT1, AMPK and retinoid-related orphan receptor alpha (RORα). SR1001, a specific inhibitor of RORα, protected the cells from light-induced activation of autophagy. Moreover, light exposure increased glucocorticoid receptor (GR) phosphorylation and nuclear translocation. GR inhibitor RU486 prevented light-induced up-regulation of RORα and the activation of autophagy. These changes were associated with enhanced glycogen synthase kinase-3 (GSK-3) activity and its specific inhibitor CHIR-99021 significantly rescued light-induced autophagy and augmented GR, RORα and autophagy-related proteins. Furthermore, GSK-3 was identified as an upstream regulator of GR/RORα signaling as it was not affected by GR or RORα inhibitors. Taken together, our data demonstrate that GSK-3-mediated GR/RORα signaling pathway is involved in white LED light-induced autophagy in hippocampal neuron cells.