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Differential Activation of Signaling Pathways by UVA and UVB Radiation in Normal Human Epidermal Keratinocytes

Authors


  • This paper is part of the Special Issue in Commemoration of the 70th birthday of Dr. David R. Bickers.

Corresponding author email: hmukhtar@wisc.edu (Hasan Mukhtar)

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 Th183/Tyr185, STAT3 at Ser727, AKT at Ser473 and increases c-Fos expression, whereas exposure to UVA, but not UVB, phosphorylates AKT at Thr308. UVB as well as UVA exposure leads to increased phosphorylation of (1) ERK1/2 at Th202/Tyr204; (2) p38 at Th180/Tyr204; (3) STAT3 at Tyr705; (4) mTOR at Thr2448; and (v) p70S6k at Thr421/Ser424; 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.

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