title: Cell fate regulated by nuclear factor-κB- and activator protein-1-dependent signalling in human melanocytes exposed to ultraviolet A and ultraviolet B.
abstract: BACKGROUND
  Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation.
  
  
  OBJECTIVE
  To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes.
  
  
  METHODS
  Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied.
  
  
  RESULTS
  UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis.
  
  
  CONCLUSIONS
  We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression.
authors.affiliation: Divison of Experimental Pathology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, S-581 85, Linköping, Sweden; Divison of Dermatology and Venereology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, S-581 85, Linköping, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Wäster
authors.forename: I
authors.initials: I
authors.lastname: Rosdahl
authors.forename: K
authors.initials: K
authors.lastname: Öllinger
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D053148:Caspase 3 / Q000378:metabolism / Q000528:radiation effects; D002478:Cells, Cultured; D004249:DNA Damage / Q000528:radiation effects; D006801:Humans; D008544:Melanocytes / Q000378:metabolism* / Q000528:radiation effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000502:physiology* / Q000528:radiation effects; D018384:Oxidative Stress / Q000528:radiation effects; D010455:Peptides / Q000494:pharmacology; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism / Q000528:radiation effects; D015398:Signal Transduction / Q000528:radiation effects; D018808:Transcription Factor AP-1 / Q000502:physiology* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D016328:NF-kappa B; D010455:Peptides; D016755:Proto-Oncogene Proteins c-jun; C118258:SN50 peptide; D018808:Transcription Factor AP-1; D053148:Caspase 3