Ultraviolet (UV) A- and UVB-induced redox alterations and activation of nuclear factor-kappaB in human melanocytes - protective effects of alpha-tocopherol

• 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.

Nyckelord

α-tocopherol

β-carotene

melanocyte nuclear factor-κB

reduced glutathione (GSH)

ultraviolet A

ultraviolet B

MEDICINE

MEDICIN

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