期刊
JOURNAL OF CELL SCIENCE
卷 126, 期 24, 页码 5578-5584出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.130633
关键词
Keratinocyte; UV irradiation; Lysosome; Cathepsin; Endocytosis; Apoptosis
类别
资金
- Swedish Research Council
- Ostergotland lans Landsting
- Welander-Finsen Foundation
- Swedish Cancer Society [2011/636]
Ultraviolet (UV) irradiation is a major environmental carcinogen involved in the development of skin cancer. To elucidate the initial signaling during UV-induced damage in human keratinocytes, we investigated lysosomal exocytosis and apoptosis induction. UVA, but not UVB, induced plasma membrane damage, which was repaired by Ca2+-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in extracellular release of cathepsin D and acid sphingomyelinase (aSMase). Two hours after UVA irradiation, we detected activation of caspase-8, which was reduced by addition of anti-aSMAse. Furthermore, caspase-8 activation and apoptosis was reduced by prevention of endocytosis and by the use of cathepsin inhibitors. We conclude that lysosomal exocytosis is part of the keratinocyte response to UVA and is followed by cathepsin-dependent activation of caspase-8. The findings have implications for the understanding of UV-induced skin damage and emphasize that UVA and UVB initiate apoptosis through different signaling pathways in keratinocytes.
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