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.

Chronic high fat diet induces cardiac hypertrophy and fibrosis in mice

“…Interfering in these processes may affect the intrinsic environment in the heart. Interestingly, GSK-3β activation is known to increase apoptosis and decrease autophagy [15,16]. …”

“…It is not known whether HFD affects these two processes in the heart. Of note, GSK-3β can regulate apoptosis and autophagy [15,16]. …”

Lithium and Autophagy

“…In epidermal cells, ultraviolet B activated autophagy as a protective response and inhibited GSK3β activation by simultaneously enhancing phosphorylation at Ser 9 . 28 In acquired cadmium resistance, lithium augmented phosphorylation at Ser 9 and increased autophagy while Thr 216 inhibited autophagy. 29 Interestingly, under serum starvation condition, GSK3β suppression with chemical inhibitors or siRNAs induced cell death, enhanced autophagy and resulted in bax interacting factor 1 (Bif-1) protein levels, 30 although Ser 9 phosphorylation has not been described.…”

“…It is likely that GSK3β negatively regulates autophagy 28,29 ( Figure 2). GSK3 activity is regulated by sitespecific phosphorylation.…”

Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species

“…Liu et al illustrated that UVB repressed the autophagic flux in A431 cells via the autophagy-repressive signaling pathway [26]. However, Yang et al found that UVB induced autophagy in JB6 epidermal cells through the GSK3b/AMPK pathway, and Chen et al illustrated that UV induced an on-rate autophagic flux in A549 and H1299 cells [27, 28]. Based on these findings, we speculated that the influence of UVB-irradiation on the cellular autophagic flux depended on the characteristic features of the cell types and the UVB-SIPS model.…”