Lysosomal exocytosis repairs the plasma membrane after UVA and is followed by caspase-8 induced apoptosis
(English)Manuscript (preprint) (Other academic)
Ultraviolet (UV)-irradiation is the major environmental carcinogen responsible for the development of skin cancer, although the mechanism is still not fully understood. In order to elucidate the early events of UVA-induced damage in human keratinocytes, we studied the initial signaling, involving caspase-8 activation and initiation of apoptosis after plasma membrane damage. We found that UVA irradiation resulted in plasma membrane damage, which was repaired by Ca2+-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in exposure of the luminal part of lysosomal associated membrane protein-1 (LAMP-1) on the plasma membrane and release of cathepsin D extracellularly. Subsequently, active caspase-8 was detected in vesicles containing the endosomal markers Rab5A and early endosomal antigen 1 (EEA1), as well as the lysosomal markers cathepsin D and LAMP-1. Inhibition of cathepsins and increase of lysosomal pH reduced caspase-8 activation and apoptosis. The findings contribute to increase our understanding of UVA-induced skin damage by emphasizing the effect of lysosomal exocytosis and release of lysosomal content outside the keratinocyte.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-85005OAI: oai:DiVA.org:liu-85005DiVA: diva2:563517