A common pathway for age-related protein oxidation and photoageing

Sarah Thurstan, Rachel EB Watson, CEM Griffiths, Neil Gibbs, Michael J Sherratt

Research output: Contribution to conferencePoster

Abstract

Remodelling of extracellular matrix (ECM) proteins as a result of solar ultraviolet radiation (UVR) exposure plays a key role in skin photoageing. We have recently demonstrated that UVR-chromophore-rich fibrillin microfibrils undergo photodegradation following UV irradiation in a cell-free environment. In this study, we test the hypotheses that fibrillin microfibril degradation following UVR exposure: i) occurs via the photodynamic production of reactive oxygen species (ROS) and; ii) alters the susceptibility of resultant microfibril photoproducts to protease-mediated degradation. Fibrillin microfibrils were isolated from cultured human dermal fibroblasts. Microfibril structure after UVB irradiation (Phillips TL-12 source; 500mJ/cm2) in ambient and O2-depleted conditions or after treatment with H2O2 (40mM; up to 2hrs) was quantified by atomic force microscopy (AFM). The effect of UVB irradiation (50mJ/cm2) on the susceptibility of microfibrils to MMP-3 proteolysis was also quantified by AFM. In ambient oxygen, UVB irradiation caused a dose-dependent decrease in median fibrillin microfibril flexion angle. However, in an O2-depleted environment the UVB mediated effects were significantly abrogated. Structural changes were mimicked by exposure to H2O2. Individually, UVB or MMP-3 significantly decreased the median microfibril flexion angle. However, addition of MMP-3 to UVB irradiated microfibrils appeared to selectively degrade low flexion angle fibrillin microfibrils leaving a population with a median flexion angle that was not significantly different to the controls. These observations suggest that UVB degradation involves the photodynamic formation of ROS and that exposure to H2O2 can mimic the effects of UVB degradation. Furthermore, MMP-3 appears to selectively degrade UVB-damaged fibrillin microfibrils in vitro
Original languageEnglish
PagesS104-S104
Publication statusPublished - 7 Sep 2011
Event41st Annual Meeting of the European Society for Dermatological Research - Barcelona, SPAIN
Duration: 7 Sep 201210 Sep 2012

Conference

Conference41st Annual Meeting of the European Society for Dermatological Research
CityBarcelona, SPAIN
Period7/09/1210/09/12

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