Activation of NF-kappa B in human skin fibroblasts by the oxidative stress generated by UVA radiation.
We have examined the role of the nucleus and the membrane in the activation of nuclear factor (NF)-kappa B by oxidant stress generated via the UVA (320-380 nm) component of solar radiation. Nuclear extracts from human skin fibroblasts that had been irradiated with UVA at doses that caused little DNA damage contained activated NF-kappa B that bound to its recognition sequence in DNA. The UVA radiation-dependent activation of NF-kappa B in enucleated cells confirmed that the nucleus was not involved. On the other hand, UVA radiation-dependent activation of NF-kappa B appeared to be correlated with membrane damage, and activation could be prevented by alpha-tocopherol and butylated hydroxytoluene, agents that inhibited UVA radiation-dependent peroxidation of cell membrane lipids. The activation of NF-kappa B by the DNA damaging agents UVC (200-290 nm) and UVB (290-320 nm) radiation also only occurred at doses where significant membrane damage was induced, and, overall, activation was not correlated with the relative levels of DNA damage induced by UVC/UVB and UVA radiations. We conclude that the oxidative modification of membrane components may be an important factor to consider in the UV radiation-dependent activation of NF-kappa B over all wavelength ranges examined.
Vile
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Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.
Tanew-Ilitschew
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A
Tyrrell
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RM
D005347:Fibroblasts / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D016328:NF-kappa B / Q000502:physiology* / Q000528:radiation effects; D018384:Oxidative Stress / Q000502:physiology* / Q000528:radiation effects; D012867:Skin / Q000528:radiation effects*; D012879:Skin Physiological Phenomena; D014466:Ultraviolet Rays
D016328:NF-kappa B