This paper is part of a special issue dedicated to Professor Hasan Mukhtar on the occasion of his 60th birthday.
Cross-validation of Murine UV Signal Transduction Pathways in Human Skin†
Article first published online: 31 JAN 2008
© 2007 The Authors
Photochemistry and Photobiology
Volume 84, Issue 2, pages 463–476, March/April 2008
How to Cite
Einspahr, J. G., Timothy Bowden, G., Alberts, D. S., McKenzie, N., Saboda, K., Warneke, J., Salasche, S., Ranger-Moore, J., Curiel-Lewandrowski, C., Nagle, R. B., Nickoloff, B. J., Brooks, C., Dong, Z. and Stratton, S. P. (2008), Cross-validation of Murine UV Signal Transduction Pathways in Human Skin. Photochemistry and Photobiology, 84: 463–476. doi: 10.1111/j.1751-1097.2007.00287.x
- Issue published online: 31 JAN 2008
- Article first published online: 31 JAN 2008
- Received 15 October 2007, accepted 5 December 2007
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.