title: Lysosomal exocytosis and caspase-8-mediated apoptosis in UVA-irradiated keratinocytes.
abstract: 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 Ca(2+)-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.
authors.affiliation: Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Appelqvist
authors.forename: Petra
authors.initials: P
authors.lastname: Wäster
authors.forename: Ida
authors.initials: I
authors.lastname: Eriksson
authors.forename: Inger
authors.initials: I
authors.lastname: Rosdahl
authors.forename: Karin
authors.initials: K
authors.lastname: Ollinger
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D053181:Caspase 8 / Q000378:metabolism*; D002402:Cathepsin D / Q000378:metabolism; D002478:Cells, Cultured; D002675:Child, Preschool; D004789:Enzyme Activation / Q000528:radiation effects; D005089:Exocytosis; D006801:Humans; D007223:Infant; D015603:Keratinocytes / Q000201:enzymology* / Q000502:physiology / Q000528:radiation effects; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress; D021381:Protein Transport; D015398:Signal Transduction; D014466:Ultraviolet Rays; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D053181:Caspase 8; D002402:Cathepsin D; D051907:Lysosomal Membrane Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C505530:CASP8 protein, human; C533922:CTSD protein, human
keywords: Apoptosis; Cathepsin; Endocytosis; Keratinocyte; Lysosome; UV irradiation