Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes
| Autor: | Petra Wäster, Inger Rosdahl, Karin Öllinger, Ida Eriksson, Hanna Appelqvist |
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| Rok vydání: | 2013 |
| Předmět: |
Keratinocytes
Male Medicin och hälsovetenskap Ultraviolet Rays Cathepsin D Apoptosis Biology Caspase 8 Endocytosis Medical and Health Sciences Exocytosis Lysosome medicine Humans Cells Cultured Cathepsin Infant Lysosome-Associated Membrane Glycoproteins Cell Biology Cell biology Enzyme Activation Keratinocyte UV irradiation Oxidative Stress Protein Transport medicine.anatomical_structure Child Preschool sense organs Signal transduction Acid sphingomyelinase Lysosomes medicine.drug Signal Transduction |
| Zdroj: | Journal of cell science. 126(Pt 24) |
| ISSN: | 1477-9137 |
| Popis: | 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. The previous status of this article was manuscript with the title Lysosomal exocytosis repairs the plasma membrane after UVA and is followed by caspase-8 induced apoptosis. |
| Databáze: | OpenAIRE |
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