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

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.