Gsk3 Beta Signaling Is Involved In Ultraviolet B-Induced Activation Of Autophagy In Epidermal Cells

Ultraviolet B (UVB) exposure causes damage to skin and represents the primary etiological agent for skin cancer formation. UVB induces DNA damage and apoptosis in epidermal cells. In this study, we demonstrated that UVB activated autophagy in JB6 epidermal cells, which was evident by the formation of LC3 puncta, the induction of LC3 lipidation, the increase in beclin 1 expression, and the decrease in the levels of p62. Autophagy appeared to be a protective response to UVB-induced damage because inhibition of autophagy exacerbated UVB-induced cell death, and stimulation of autophagy offered protection. Furthermore, we demonstrated that glycogen synthase kinase 3 beta (GSK3 beta) was involved in UVB-induced autophagy. UVB inhibited GSK3 beta activation by simultaneously enhancing phosphorylation at Ser(9) and suppressing Tyr(216) phosphorylation. GSK3 beta negatively regulated autophagy; overexpression of wild-type or S9A (constitutive-active) GSK3 beta mutant inhibited UVB-mediated autophagy, while overexpression of a dominant-negative K85R mutant enhanced UVB-mediated autophagy. Inhibition of GSK3 beta also offered protection against UVB-mediated damage. UVB activated AMP-activated protein kinase (AMPK), an important regulator of autophagy through the inhibition of GSK3 beta. Taken together, our results suggest that UVB-stimulated autophagy is a protective response for epidermal cells and is mediated by the GSK3 beta/AMPK pathway.