A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues.
Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm(2)) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage.
Centre for Dermatology Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Sarah A
SA
Hibbert
Centre for Dermatology Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Rachel E B
REB
Watson
Centre for Dermatology Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Neil K
NK
Gibbs
Centre for Dermatology Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Patrick
P
Costello
Faculty of Life Sciences, Wellcome Trust Centre for Cell-Matrix Research, The University of Manchester, Manchester, UK.
Clair
C
Baldock
School of Molecular Bioscience, The University of Sydney, Sydney, Australia; Charles Perkins Centre, The University of Sydney, Sydney, Australia; Bosch Institute, The University of Sydney, Sydney, Australia.
Anthony S
AS
Weiss
Centre for Dermatology Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Christopher E M
CEM
Griffiths
Centre for Tissue Injury and Repair, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. Electronic address: michael.sherratt@manchester.ac.uk.
Michael J
MJ
Sherratt
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002417:Cattle; D024042:Collagen Type I / Q000737:chemistry / Q000378:metabolism; D024142:Collagen Type VI / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D005109:Extracellular Matrix / Q000378:metabolism; D000071837:Fibrillins; D005353:Fibronectins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000378:metabolism; D008840:Microfilament Proteins / Q000378:metabolism / Q000648:ultrastructure; D018625:Microscopy, Atomic Force; D012867:Skin / Q000378:metabolism* / Q000528:radiation effects; D014333:Tropoelastin / Q000737:chemistry / Q000378:metabolism; D014466:Ultraviolet Rays; D038201:alpha-Crystallins / Q000737:chemistry / Q000378:metabolism
D000975:Antioxidants; D024042:Collagen Type I; D024142:Collagen Type VI; D000071837:Fibrillins; D005353:Fibronectins; D008543:Melanins; D008840:Microfilament Proteins; D014333:Tropoelastin; D038201:alpha-Crystallins
Chromophores; Photoageing; Photodecomposition; Solar simulated radiation; Sunscreen; UVA radiation