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

  • Authors:
    • Yang Yang
    • Haiping Wang
    • Siying Wang
    • Mei Xu
    • Mei Liu
    • Mingjun Liao
    • Jacqueline A. Frank
    • Sabal Adhikari
    • Kimberly A. Bower
    • Xianglin Shi
    • Cuiling Ma
    • Jia Luo
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  • Published online on: September 5, 2012     https://doi.org/10.3892/ijo.2012.1620
  • Pages: 1782-1788
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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.
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November 2012
Volume 41 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Yang Y, Wang H, Wang S, Xu M, Liu M, Liao M, Frank JA, Adhikari S, Bower KA, Shi X, Shi X, et al: GSK3β signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells. Int J Oncol 41: 1782-1788, 2012
APA
Yang, Y., Wang, H., Wang, S., Xu, M., Liu, M., Liao, M. ... Luo, J. (2012). GSK3β signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells. International Journal of Oncology, 41, 1782-1788. https://doi.org/10.3892/ijo.2012.1620
MLA
Yang, Y., Wang, H., Wang, S., Xu, M., Liu, M., Liao, M., Frank, J. A., Adhikari, S., Bower, K. A., Shi, X., Ma, C., Luo, J."GSK3β signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells". International Journal of Oncology 41.5 (2012): 1782-1788.
Chicago
Yang, Y., Wang, H., Wang, S., Xu, M., Liu, M., Liao, M., Frank, J. A., Adhikari, S., Bower, K. A., Shi, X., Ma, C., Luo, J."GSK3β signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells". International Journal of Oncology 41, no. 5 (2012): 1782-1788. https://doi.org/10.3892/ijo.2012.1620