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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Differential activation of signaling pathways by UVA and UVB radiation in normal human epidermal keratinocytes.

Authors: Syed, Deeba N; Afaq, Farrukh; Mukhtar, Hasan

Published In Photochem Photobiol, (2012 Sep-Oct)

Abstract: Ultraviolet (UV) radiation from the solar spectrum is a major etiological factor for many cutaneous pathologies including cancer. By understanding changes in cell signaling pathways induced by UVA and UVB, novel strategies for prevention and treatment of UV-related pathologies could be developed. However, much of the information in the literature from various laboratories cannot cross talk because of difficulties associated with the use of ill-defined light sources and physiologically irrelevant light dosimetry. Herein, we have assessed the effect of exposure of normal human epidermal keratinocytes (NHEK) to UVA (2 and 4 J cm(-2)) or UVB (20 and 40 mJ cm(-2)) radiation. Employing western blot analysis, we found that exposure of NHEK to UVB, but not UVA, phosphorylates JNK1/2 at Th(183)/Tyr(185), STAT3 at Ser(727) , AKT at Ser(473) and increases c-Fos expression, whereas exposure to UVA, but not UVB, phosphorylates AKT at Thr(308). UVB as well as UVA exposure leads to increased phosphorylation of (1) ERK1/2 at Th(202)/Tyr(204); (2) p38 at Th(180)/Tyr(204); (3) STAT3 at Tyr(705); (4) mTOR at Thr(2448); and (v) p70S6k at Thr(421) /Ser(424); enhanced expression of PI3K (p85) and c-jun; and nuclear translocation of NFκB proteins. These findings could be considered as a beginning for understanding the differential effects of UVA and UVB in the human skin and may have implications both with respect to risk assessment from exposure to solar UV radiation, and to target interventions against signaling events mediated by UVA and UVB.

PubMed ID: 22335604 Exiting the NIEHS site

MeSH Terms: Biomarkers/metabolism; Blotting, Western; Epidermis/cytology; Epidermis/radiation effects*; Gene Expression/radiation effects*; Humans; Keratinocytes/cytology; Keratinocytes/radiation effects*; Mitogen-Activated Protein Kinase 8/genetics; Mitogen-Activated Protein Kinase 8/metabolism; Mitogen-Activated Protein Kinase 9/genetics; Mitogen-Activated Protein Kinase 9/metabolism; NF-kappa B/genetics; NF-kappa B/metabolism; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism; Phosphorylation; Primary Cell Culture; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; Proto-Oncogene Proteins c-fos/genetics; Proto-Oncogene Proteins c-fos/metabolism; Radiometry; STAT3 Transcription Factor/genetics; STAT3 Transcription Factor/metabolism; Signal Transduction/radiation effects*; TOR Serine-Threonine Kinases/genetics; TOR Serine-Threonine Kinases/metabolism; Ultraviolet Rays/adverse effects*; Ultraviolet Rays/classification

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