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

FEBS Letters

Vandenheede, Jackie R³  Garmyn, Marjan²  Vandenabeele, Peter¹  Agostinis, Patrizia³  Assefa, Zerihun³  Vantieghem, Annelies³  Declercq, Wim¹ 

[1] Department of Molecular Biomedical Research, VIB, University of Gent, Ledeganckstraat 35, B-9000 Gent, Belgium;Laboratory of Dermatology, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven, Belgium;Division of Biochemistry, Faculty of Medicine, Catholic University of Leuven, Herestraat 49, B-3000 Leuven, Belgium

关键词: Ultraviolet radiation;    Apoptosis;    Bcl-2;    Caspase;    Keratinocyte;    UV;    ultraviolet;    FasL;    Fas ligand;    DISC;    death-inducing signaling complex;    ROS;    reactive oxygen species;    NAO;    nonyl acridine orange;    AO;    acridine orange;    carboxy-H2DCFDA;    carboxy-2′;    7′-dichlorodihydrofluorescin diacetate;   

DOI  :  10.1016/S0014-5793(03)00238-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown