Skin oxi-proteome protection against uva/uvb using the vitamin e prodrug delta-tocopherol glucoside

Summary: Abstract Body: The aim of this study was to investigate the protective efficacy of the vitamin E prodrug delta-tocopherol glucoside (delta-TG) against oxidative damage induced by UVA/UVB. Using mass spectrometry-based non-targeted oxi-proteomics, we analyzed the oxidation patterns of proteins in keratinocytes after UV irradiation at 1 MED, and the protective effect of delta-TG. After UV irradiation, 273 proteins were significantly oxidized with 12 modification patterns, including carbonylation, tryptophan conversion, and 4-hydroxynonenal modification. Delta-TG treatment significantly protected 44% of these modified proteins from UV-induced oxidation. Analysis of the 120 protected proteins revealed a highly connected network, with subnetworks involved in epidermal structure (e.g., KRT5, KRT14, PLEC), cytoskeleton (e.g., ACTN1, JUP, CTNNA1), collagen chaperones (e.g., SERPINH1, P4HB, THBS1), and mRNA splicing regulation (e.g., HNRPL, HNRPD, PRPF8). These data highlight broad protection by delta-TG, from protein structure to essential tissue functions. Notably, plectin, crucial for epidermal-dermis junctions and a biomarker for several cancers including squamous cell carcinoma, was significantly protected from oxidative damage, as were its interacting proteins like Laminin 332. This study shows that oxi-proteome analysis can guide the development of effective sunscreens, with specific antioxidants to prevent cellular and tissue damage. In conclusion, delta-TG is an excellent candidate for reinforcing skin antioxidants, especially to prevent UV-induced protein oxidation. These results support further research into optimizing suncare formulations with antioxidants like delta-TG. Benoit Beganton¹, Daniel Bacqueville¹, Carine Jacques-Jamin¹, Jérémy Sereno¹, Camille Boudet², Gautier Doat², Sandrine Bessou-Touya¹, Hélène Duplan¹ 1. Recherche Pharmaco-Clinique, Pierre Fabre Dermo-Cosmetique SAS, Toulouse, Occitanie, France. 2. Laboratoires Avène, Lavaur, France. UV Biology/Injury and Non-melanoma Cancers