GSK3β signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells

Ultraviolet B (UVB) exposure causes damage to skin and represents the primaryetiological agent for skin cancer formation. UVB induces DNA damage and apoptosisin epidermal cells. In this study, we demonstrated that UVB activated autophagyin JB6 epidermal cells, which was evident by the formation of LC3 puncta, theinduction of LC3 lipidation, the increase in beclin 1 expression, and the decreasein the levels of p62. Autophagy appeared to be a protective response to UVB-induceddamage because inhibition of autophagy exacerbated UVB-induced cell death, andstimulation of autophagy offered protection. Furthermore, we demonstrated thatglycogen synthase kinase 3β (GSK3β) was involved in UVB-induced autophagy. UVBinhibited GSK3β activation by simultaneously enhancing phosphorylation at Ser9and suppressing Tyr216 phosphorylation. GSK3β negatively regulated autophagy;overexpression of wild‑type or S9A (constitutive-active) GSK3β mutant inhibitedUVB-mediated autophagy, while overexpression of a dominant-negative K85R mutantenhanced UVB-mediated autophagy. Inhibition of GSK3β also offered protection againstUVB-mediated damage. UVB activated AMP-activated protein kinase (AMPK), an importantregulator of autophagy through the inhibition of GSK3β. Taken together, our resultssuggest that UVB-stimulated autophagy is a protective response for epidermal cellsand is mediated by the GSK3β/AMPK pathway.