Ultraviolet B radiation-induced apoptosis in human keratinocytes: cytosolic activation of procaspase-8 and the role of Bcl-2

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, mitochon...

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Bibliographic Details
Published in:FEBS letters 2003-04, Vol.540 (1), p.125-132
Main Authors: Assefa, Zerihun, Garmyn, Marjan, Vantieghem, Annelies, Declercq, Wim, Vandenabeele, Peter, Vandenheede, Jackie R, Agostinis, Patrizia
Format: Article
Language:English
Subjects:
AO, acridine orange
Apoptosis
Apoptosis - physiology
Apoptosis - radiation effects
Bcl-2
carboxy-H2DCFDA, carboxy-2′,7′-dichlorodihydrofluorescin diacetate
Caspase
Caspase 8
Caspase 9
Caspases - metabolism
Cell Line
Cytosol - enzymology
DISC, death-inducing signaling complex
Enzyme Activation
Enzyme Precursors - metabolism
FasL, Fas ligand
Humans
Keratinocyte
Keratinocytes - cytology
Keratinocytes - radiation effects
NAO, nonyl acridine orange
Proto-Oncogene Proteins c-bcl-2 - physiology
ROS, reactive oxygen species
Ultraviolet radiation
Ultraviolet Rays
UV, ultraviolet
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Summary: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
1873-3468
DOI:10.1016/S0014-5793(03)00238-2