Cross-validation of murine UV signal transduction pathways in human skin

Janine G Einspahr, G. Timothy Bowden, David S Alberts, Naja McKenzie, Kathylynn Saboda, James A Warneke, Stuart Salasche, James Ranger-Moore, Clara N Curiel, Raymond B Nagle, Brian J. Nickoloff, Christine Brooks, Zigang Dong, Steven P Stratton

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

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 4x 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.

Original languageEnglish (US)
Pages (from-to)463-476
Number of pages14
JournalPhotochemistry and Photobiology
Volume84
Issue number2
DOIs
StatePublished - Mar 2008

Fingerprint

Signal transduction
Glycogen Synthase Kinase 3
Signal Transduction
Skin
phosphorylation
apoptosis
proteins
Phosphorylation
mice
MAP Kinase Kinase 3
activation
Apoptosis
epidermis
Chemical activation
Chemoprevention
Skin Neoplasms
p38 Mitogen-Activated Protein Kinases
Epidermis
genes
Biopsy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Biophysics

Cite this

Cross-validation of murine UV signal transduction pathways in human skin. / Einspahr, Janine G; Timothy Bowden, G.; Alberts, David S; McKenzie, Naja; Saboda, Kathylynn; Warneke, James A; Salasche, Stuart; Ranger-Moore, James; Curiel, Clara N; Nagle, Raymond B; Nickoloff, Brian J.; Brooks, Christine; Dong, Zigang; Stratton, Steven P.

In: Photochemistry and Photobiology, Vol. 84, No. 2, 03.2008, p. 463-476.

Research output: Contribution to journalArticle

Einspahr, Janine G ; Timothy Bowden, G. ; Alberts, David S ; McKenzie, Naja ; Saboda, Kathylynn ; Warneke, James A ; Salasche, Stuart ; Ranger-Moore, James ; Curiel, Clara N ; Nagle, Raymond B ; Nickoloff, Brian J. ; Brooks, Christine ; Dong, Zigang ; Stratton, Steven P. / Cross-validation of murine UV signal transduction pathways in human skin. In: Photochemistry and Photobiology. 2008 ; Vol. 84, No. 2. pp. 463-476.
@article{27902ae5e42a4892b5689107f9246866,
title = "Cross-validation of murine UV signal transduction pathways in human skin",
abstract = "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 4x 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.",
author = "Einspahr, {Janine G} and {Timothy Bowden}, G. and Alberts, {David S} and Naja McKenzie and Kathylynn Saboda and Warneke, {James A} and Stuart Salasche and James Ranger-Moore and Curiel, {Clara N} and Nagle, {Raymond B} and Nickoloff, {Brian J.} and Christine Brooks and Zigang Dong and Stratton, {Steven P}",
year = "2008",
month = "3",
doi = "10.1111/j.1751-1097.2007.00287.x",
language = "English (US)",
volume = "84",
pages = "463--476",
journal = "Photochemistry and Photobiology",
issn = "0031-8655",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Cross-validation of murine UV signal transduction pathways in human skin

AU - Einspahr, Janine G

AU - Timothy Bowden, G.

AU - Alberts, David S

AU - McKenzie, Naja

AU - Saboda, Kathylynn

AU - Warneke, James A

AU - Salasche, Stuart

AU - Ranger-Moore, James

AU - Curiel, Clara N

AU - Nagle, Raymond B

AU - Nickoloff, Brian J.

AU - Brooks, Christine

AU - Dong, Zigang

AU - Stratton, Steven P

PY - 2008/3

Y1 - 2008/3

N2 - 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 4x 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.

AB - 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 4x 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.

UR - http://www.scopus.com/inward/record.url?scp=41049117630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41049117630&partnerID=8YFLogxK

U2 - 10.1111/j.1751-1097.2007.00287.x

DO - 10.1111/j.1751-1097.2007.00287.x

M3 - Article

VL - 84

SP - 463

EP - 476

JO - Photochemistry and Photobiology

JF - Photochemistry and Photobiology

SN - 0031-8655

IS - 2

ER -