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Title: Ultraviolet B radiation-induced apoptosis in human keratinocytes: cytosolic activation of procaspase-8 and the role of Bcl-2
Authors: Assefa, Zerihun ×
Garmyn, Maria
Vantieghem, Annelies
Declercq, Wim
Vandenabeele, Peter
Vandenheede, Jackie
Agostinis, Patrizia #
Issue Date: Apr-2003
Publisher: Elsevier on behalf of the Federation of European Biochemical Societies
Series Title: FEBS Letters vol:540 issue:1-3 pages:125-32
Abstract: In this study, we show that ultraviolet B radiation (UVB)-induced apoptosis of human keratinocytes involves mainly cytosolic signals with mitochondria playing a central role. Overexpression of Bcl-2 inhibited UVB-induced apoptosis by blocking the early generation of reactive oxygen species, mitochondrial cardiolipin degradation and cytochrome c release, without affecting Fas ligand (FasL)-induced cell death. It also prevented the subsequent activation of procaspase-3 and -8 as well as Bid cleavage in UVB-treated cells. Comparative analysis of UVB and FasL death pathways revealed a differential role and mechanism of caspase activation, with the UVB-induced activation of procaspase-8 only being a bystander cytosolic event rather than a major initiator mechanism, as is the case for the FasL-induced cell death. Our results suggest that Bcl-2 overexpression, by preventing reactive oxygen species production, helps indirectly to maintain the integrity of lysosomal membranes, and therefore inhibits the release of cathepsins, which contribute to the cytosolic activation of procaspase-8 in UVB-irradiated keratinocytes.
ISSN: 0014-5793
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry Section (Medicine) (-)
Laboratory of Dermatology
Laboratory of Cell Death Research & Therapy
× corresponding author
# (joint) last author

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