Ultraviolet irradiation increases FADD protein in apoptotic human keratinocytes |
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Authors: | Kim Peter K M Weller Richard Hua Yun Billiar Timothy R |
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Institution: | Department of Surgery, University of Pittsburgh Medical Center, NW607 MUH, Pittsburgh, PA 15213, USA. kimp@msx.upmc.edu |
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Abstract: | Ultraviolet irradiation (UV) can induce keratinocyte apoptosis by activating death receptors that recruit the intracellular adaptor molecule FADD/MORT1 (Fas-associating death domain protein/mediator of receptor-induced toxicity). We hypothesized that UV could alter FADD expression levels to augment UV-induced keratinocyte apoptosis. In a dose-dependent manner UV B irradiation increased the expression of FADD protein in a human keratinocyte cell line (CCD-1106) with a corresponding increase in caspase-8 cleavage and cellular apoptosis. FADD overexpression induced cell death in 80% of cells compared with 10% spontaneous cell death in controls. Inhibition of FADD protein by adenoviral expression of anti-sense FADD reduced keratinocyte apoptosis. Regulation of FADD expression by UV may serve to enhance death receptor-mediated keratinocyte death. |
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Keywords: | Apoptosis FADD MORT1 Keratinocyte Ultraviolet irradiation |
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