Ultraviolet irradiation increases FADD protein in apoptotic human keratinocytes.
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.
Kim
Peter K M
PK
Department of Surgery, University of Pittsburgh Medical Center, NW607 MUH, Pittsburgh, PA 15213, USA. kimp@msx.upmc.edu
Weller
Richard
R
Hua
Yun
Y
Billiar
Timothy R
TR
D017209:Apoptosis / Q000502:physiology*; D029681:Arabidopsis Proteins; D002470:Cell Survival / Q000528:radiation effects; D002478:Cells, Cultured; D044943:Fatty Acid Desaturases / Q000378:metabolism*; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects*; D014466:Ultraviolet Rays
D029681:Arabidopsis Proteins; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis