A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

Abstract

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/cm2) 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.

Evolutionary Origins of Pax6 Control of Crystallin Genes

“…2011 ). It is also possible that β/γ-crystallins originally served as UV light filters ( Hibbert etal. 2015 ).…”

Secondary Plant Metabolites for Sun Protective Cosmetics: From Pre-Selection to Product Formulation

“…This interaction reduces UV penetration, hence the chromophores play a protective role of sacrificial sunscreens. Recently, the utmost importance of epidermal and dermal UV chromophore rich proteins including the late cornified envelope proteins, keratin associated proteins, and elastic fibre-associated components as endogenous sacrificial sunscreens have been described [37].…”

“…The extracellular space of dermis contains large amounts of water-soluble antioxidants such as ascorbic acid, uric acid, and glutathione. In addition, several key structural proteins abundantly present in the stratum corneum, hair, and papillary dermis and characterised by the high content of aminoacids-chromophores, namely, cysteine, tryptophan, and tyrosine, appear to have significant impact on cutaneous antioxidant defence protecting skin structures against photo-chemical oxidative stress [37]. As part of an adaptive response, abnormal levels of ROS also induce the expression of ROS-detoxifying enzymes, mainly through a nuclear factor erythroid 2-related factor 2 (Nrf2)-dependent mechanism [44].…”

Heterogeneity of fibrillin‐rich microfibrils extracted from human skin of diverse ethnicity

“…Here we demonstrate that during human foetal development, FRM synthesis appears invariant irrespective of ethnic background, a finding consistent with their highly conserved evolution. These neonatal foreskin FRMs comprised both fibrillin-1 and fibrillin-2, and may represent a (Zhang et al, 1994(Zhang et al, , 1995 more akin to FRMs that are synthesized in vitro from human dermal fibroblasts (Hibbert et al, 2015). A potential limitation of these data is the assumption that neonatal foreskin represents a faithful model of adult photoprotected skin.…”

“…Periodicity was determined by measuring the distance between individual beads (n = 1000 for adult samples; n = 250 for foreskin samples) using WSxM scanning probe microscopy software, and by routines written in Microsoft Visual Basic 6.0. Inter-bead periodicity is a widely used, reliable and quantitative marker for analysis of FRM ultrastructure (Sherratt et al, 2010;Hibbert et al, 2015;Eckersley et al, 2018).…”