Ultraviolet (UV) A- and UVB-induced redox alterations and activation of nuclear factor-kappaB in human melanocytes - protective effects of alpha-tocopherol
2006 (English)In: British Journal of Dermatology, ISSN 0007-0963 (print), 1365-2133 (online), Vol. 155, no 2, 292-300 p.Article in journal (Refereed) Published
Background Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge concerning reaction pathways and signalling transduction in melanocytes is still limited.
Objectives To evaluate the protective capacity of α-tocopherol and β-carotene during UVA and UVB irradiation of human melanocytes in vitro.
Methods Primary cultures of normal human melanocytes were irradiated by different wavelengths within the UV spectrum (UVA 6 J cm−2, UVB 60 mJ cm−2). Redox alterations and apoptosis were studied and the protective potential of α-tocopherol and β-carotene was evaluated.
Results UVA and UVB irradiation decreased the intracellular concentration of reduced glutathione and activated the transcription factor nuclear factor (NF)-κB, detected as the increased level of the p65 subunit and translocation to the nucleus. This coincided with a rise in the level of γ-glutamyl-cysteine-synthetase, the rate-limiting enzyme of the glutathione synthesis. UVA and UVB caused apoptotic cell death as detected by nuclear fragmentation and caspase activation 24 h postirradiation. Pretreatment with α-tocopherol prevented UVA- and UVB-induced glutathione loss, NF-κB translocation and diminished apoptosis, but β-carotene did not show a similar protective capacity. Further, exposure to α-tocopherol by itself reduced cell proliferation rate.
Conclusions UVA and UVB irradiation affected the intracellular redox state and increased the frequency of apoptosis in human melanocytes in vitro. α-Tocopherol might be a useful substance in protecting melanocytes from UV-induced damage.
Place, publisher, year, edition, pages
2006. Vol. 155, no 2, 292-300 p.
α-tocopherol, β-carotene, melanocyte nuclear factor-κB, reduced glutathione (GSH), ultraviolet A, ultraviolet B
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-14498DOI: 10.1111/j.1365-2133.2006.07347.xOAI: oai:DiVA.org:liu-14498DiVA: diva2:23597