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-3beta 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-3beta 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.

Luteolin inhibits Cr(VI)-induced malignant cell transformation of human lung epithelial cells by targeting ROS mediated multiple cell signaling pathways

“…Cr(VI) exposure in BEAS-2B cells increased Stat3 activation and phosphorylation whereas treatment of luteolin suppressed them. MAPKs are made up of three family members that include extracellular-signal-related protein kinases (ERKs), stress-activated c-JUN N-terminal (JNKs/SAPs) and p38 kinases (Einspahr et al , 2008). Previous studies have shown that Cr(VI) markedly induces MAP kinase pathways in CL3 cells and is positively correlated with oxidative stress (Chuang et al , 2000).…”

Cyanidin-3-glucoside inhibits UVB-induced oxidative damage and inflammation by regulating MAP kinase and NF-κB signaling pathways in SKH-1 hairless mice skin

“…MAPK are made up of three family members that include extracellular-signal-related protein kinases (ERKs), c-JUN N-terminal kinases stress-activated protein kinases (JNKs/SAPs) and p38 kinases (Einspahr et al , 2008). During the activation of p38MAPK, several upstream kinases, including MAP kinase kinases (MKK) are also involved.…”

Expression of CREB in Primary Pterygium and Correlation with Cyclin D1, ki-67, MMP7, p53, p63, Survivin and Vimentin

“…Among these, of particular interest are MAP kinase, PI3 kinase, p53, cyclic AMP response-element binding protein (CREB) and JNK pathways that result in the induction of expression of specific genes that can lead to skin cancer. Some of the same pathways have also been described to be activated in pterygium, suggesting a further similarity between the two processes [3,4,5,6,7]. Several reports have documented the effects of UV exposition primarily on human skin and then on normal and pathological cultured ocular surface cells [18,19,20].…”

“…Pterygia can vary from small, atrophic quiescent lesions to large, aggressive, rapidly growing fibrovascular lesions that can distort the corneal topography, and, in advanced cases, obscure the optical center of the cornea [1,2]. Both epithelial cells and fibroblasts obtained from pterygia show transformed cell-like features, with a documented faster growth in culture compared to normal conjunctiva, and share with transformed cells the activation of several pathways like p38/MAPK, p53, and PI3 kinase [3,4]. …”