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  • Title: Effect of ultraviolet radiation on the expression of pp38MAPK and furin in human keratinocyte-derived cell lines.
    Author: Huynh TT, Chan KS, Piva TJ.
    Journal: Photodermatol Photoimmunol Photomed; 2009 Feb; 25(1):20-9. PubMed ID: 19152512.
    Abstract:
    BACKGROUND: Ultraviolet radiation (UVR) is known to induce the activation of stress-inflammation signal transduction pathways, and to induce the activity of many proteases in skin cells. It is unknown whether the activation of proteases such as furin is related to changes in the phosphorylation status of p38MAPK. METHODS: The effect of UVR on immortalized keratinocyte (HaCaT) and squamous cell carcinoma (Colo16) cells was investigated with respect to cell survival, phosphorylation of p38MAPK, and the proprotein convertase, furin. The cells were exposed to either a low or a high dose of UVA and/or UVB and the viability was monitored over 48 h, along with changes in the intracellular expression of p38MAPK and furin. RESULTS: Low-dose UVA (2 kJ/m(2)) and/or UVB (0.2 kJ/m(2)) radiation had no effect on cell viability, except in UVA-irradiated Colo16 cells. High UVA (20 kJ/m(2)) caused a loss of cell viability in HaCaT cells, but not in Colo16 cells. The opposite effect was seen in cells exposed to a high UVB dose (2 kJ/m(2)). The viability of both cell cultures decreased when exposed to high-dose UVA+B radiation. UV irradiation downregulated the expression of phosphorylated p38 (pp38) in HaCaT cells irrespective of the UV dose and type. In Colo16 cells, UV radiation induced pp38 expression in the cells following exposure, with the highest increase in cells exposed to high-dose UVA. The expression of furin in UV-irradiated HaCaT cells was similar to that seen for pp38 expression. In Colo16 cells, UV radiation induced furin expression, with the highest increase seen in cells 24 h after exposure to both high-dose UVB and UVA+B radiation. CONCLUSION: The results show that there are differences between the effect of UV types and doses on cell function in the keratinocyte-derived cell lines examined in this study. The level of furin expression in Colo16 cells correlated to changes in pp38 levels in the cells following exposure to UV radiation, but not in HaCaT cells. From an improved understanding of the signalling pathways and their downstream events and how these may differ as a result of tumorigenesis, it may enable the development of inhibitors, which may have therapeutic applications.
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