GSK3β signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells.
GSK3β signaling is involved in ultraviolet B-induced activation of autophagy in epidermal cells.
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DOI：
10.3892/ijo.2012.1620
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发表时间：
2012-11
影响因子：
5.2
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Yang Y;Wang H;Wang S;Xu M;Liu M;Liao M;Frank JA;Adhikari S;Bower KA;Shi X;Ma C;Luo J
紫外线B（UVB）暴露会对皮肤造成损伤，是皮肤癌形成的主要病原体。UVB诱导表皮细胞DNA损伤和凋亡。在这项研究中，我们证明，UVB激活自噬在JB 6表皮细胞，这是显而易见的形成LC 3斑点，诱导LC 3脂化，增加beclin 1的表达，并在p62的水平下降。自噬似乎是对UVB诱导的损伤的保护性反应，因为抑制自噬加剧UVB诱导的细胞死亡，而刺激自噬提供保护。此外，我们证明糖原合成酶激酶3β（GSK 3 β）参与UVB诱导的自噬。UVB通过同时增强Ser 9的磷酸化和抑制Tyr 216的磷酸化来抑制GSK 3 β的活化。GSK 3 β负性调节自噬;野生型或S9 A（组成型活性）GSK 3 β突变体的过表达抑制UVB介导的自噬，而显性负性K85 R突变体的过表达增强UVB介导的自噬。抑制GSK 3 β也提供了对UVB介导的损伤的保护。UVB通过抑制GSK 3 β激活AMP活化蛋白激酶（AMPK），AMPK是自噬的重要调节因子。综上所述，我们的研究结果表明，UVB刺激的自噬是表皮细胞的保护性反应，并由GSK 3 β/AMPK通路介导。
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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DOI：
10.2217/14796694.2.1.91
发表时间：
2006-02-01
期刊：
Future oncology (London, England)
影响因子：
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作者：
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影响因子：
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作者：
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影响因子：
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作者：
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DOI：
10.1016/j.bbamcr.2008.12.013
发表时间：
2009-09
期刊：
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