Premium
Cross‐validation of Murine UV Signal Transduction Pathways in Human Skin †
Author(s) -
Einspahr Janine G.,
Timothy Bowden G.,
Alberts David S.,
McKenzie Naja,
Saboda Kathylynn,
Warneke James,
Salasche Stuart,
RangerMoore James,
CurielLewandrowski Clara,
Nagle Raymond B.,
Nickoloff Brian J.,
Brooks Christine,
Dong Zigang,
Stratton Steven P.
Publication year - 2008
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.1751-1097.2007.00287.x
Subject(s) - creb , p38 mitogen activated protein kinases , phosphorylation , signal transduction , kinase , apoptosis , mapk/erk pathway , protein kinase a , human skin , microbiology and biotechnology , epidermis (zoology) , pi , biology , chemistry , transcription factor , gene , biochemistry , anatomy , genetics
Acute UVB irradiation of mouse skin results in activation of phospatidyinositol‐3 (PI‐3) kinase and mitogen‐activated protein kinase (MAPK) pathways leading to altered protein phosphorylation and downstream transcription of genes. We determined whether activation of these pathways also occurs in human skin exposed to 4× minimal erythemic dose of UVB in 23 volunteers. Biopsies were taken prior to, at 30 min, 1 and 24 h post‐UVB. In agreement with mouse studies, the earliest UV‐induced changes in epidermis were seen in phospho‐CREB (two‐ and five‐fold at 30 min and 1 h) and in phospho‐MAPKAPK‐2 (three‐fold at both 30 min and 1 h). At 1 h, phospho‐c‐JUN and phospho‐p38 were increased five‐ and two‐fold, respectively. Moreover, phospho‐c‐JUN and phospho‐p38 were further increased at 24 h (12‐ and six‐fold, respectively). Phospho‐GSK‐3β was similarly increased at all time points. Increases in phospho‐p53 (12‐fold), COX‐2 (four‐fold), c‐FOS (14‐fold) and apoptosis were not seen until 24 h. Our data suggest that UVB acts through MAPK p38 and PI‐3 kinase with phosphorylation of MAPKAPK‐2, CREB, c‐JUN, p38, GSK‐3β and p53 leading to marked increases in c‐FOS, COX‐2 and apoptosis. Validation of murine models in human skin will aid in development of effective skin cancer chemoprevention and prevention strategies.