• Dna Damage
    • Uvb Light Induces Nuclear...
    • UVB Light Induces Nuclear Factor κB (NFκB) Activity Independently from Chromosomal DNA Damage in Cell-Free Cytosolic Extracts: Influence Statistics

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      Concepts for whichthey havehas direct influence:Dna damage,Nf kappa,Nuclear factor,Kappa nf,Nuclear factor κb,Tumor cells,Activation nf,Uv light.

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      UVB Light Induces Nuclear Factor κB (NFκB) Activity Independently from Chromosomal DNA Damage in Cell-Free Cytosolic Extracts


      It has been shown previously that ultraviolet (UV) light (290-320 nm) activates keratinocytes to release proinflammatory cytokines including interleukin (IL)-6. Because the 5' flanking region of the IL-6 gene contains a consensus NF kappa B binding sequence, the effect of UVB light on an NF kappa B-like binding activity was investigated in a human epidermoid carcinoma cell line (A431). Nuclear factor kappa B (NF kappa B) activation in the cytoplasm is known to be due to the dissociation of an inactive NF kappa B-inhibitor of nuclear factor kappa B (I kappa B) complex. Cytosolic extracts from cells harvested shortly after sublethal UVB irradiation showed a UVB dose-dependent increase of NF kappa B binding. The activation was reduced by radical scavenging chemicals, suggesting involvement of reactive oxygen intermediates. NF kappa B activation has been shown previously to be triggered by DNA lesions induced by UV light. To elucidate whether DNA damage is necessary and sufficient to mediate NF kappa B activation crude, cytosolic protein extracts obtained from unirradiated cells were exposed to UVB light. This in vitro UVB treatment led to activation of an NF kappa B-like binding activity, suggesting an additional signaling pathway independent of chromosomal DNA damage or byproducts of DNA damage. The activation process was dependent on the presence of membranes. The data suggest at least an additional signaling pathway for the early UVB response, including a component of the pathway residing at the cell membrane.

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