title: GSK3β signaling is involved in ultraviolet B-induced activation of autophagy             in epidermal cells.
abstract: 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 3β (GSK3β) was involved in UVB-induced autophagy. UVB             inhibited GSK3β activation by simultaneously enhancing phosphorylation at Ser9             and suppressing Tyr216 phosphorylation. GSK3β negatively regulated autophagy;             overexpression of wild‑type or S9A (constitutive-active) GSK3β mutant inhibited             UVB-mediated autophagy, while overexpression of a dominant-negative K85R mutant             enhanced UVB-mediated autophagy. Inhibition of GSK3β also offered protection against             UVB-mediated damage. UVB activated AMP-activated protein kinase (AMPK), an important             regulator of autophagy through the inhibition of GSK3β. Taken together, our results             suggest that UVB-stimulated autophagy is a protective response for epidermal cells             and is mediated by the GSK3β/AMPK pathway.
authors.affiliation: Department of Internal Medicine, University of Kentucky College                     of Medicine, Lexington, KY 40536, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Haiping
authors.initials: H
authors.lastname: Wang
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Mingjun
authors.initials: M
authors.lastname: Liao
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Frank
authors.forename: Sabal
authors.initials: S
authors.lastname: Adhikari
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Bower
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Cuiling
authors.initials: C
authors.lastname: Ma
authors.forename: Jia
authors.initials: J
authors.lastname: Luo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000528:radiation effects*; D002460:Cell Line; D004817:Epidermis / Q000378:metabolism* / Q000528:radiation effects; D004847:Epithelial Cells / Q000378:metabolism* / Q000528:radiation effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D051379:Mice; D010766:Phosphorylation / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects*; D014466:Ultraviolet Rays
chemical_list: D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases