Premium
Differential Activation of Signaling Pathways by UVA and UVB Radiation in Normal Human Epidermal Keratinocytes †
Author(s) -
Syed Deeba N.,
Afaq Farrukh,
Mukhtar Hasan
Publication year - 2012
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.2012.01115.x
Subject(s) - phosphorylation , protein kinase b , human skin , pi3k/akt/mtor pathway , signal transduction , western blot , cancer research , chemistry , p38 mitogen activated protein kinases , microbiology and biotechnology , biology , biochemistry , protein kinase a , gene , genetics
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.