Photoinduced damage to proteins and their components by an endogenous sensitizer of biomedical interest

M. LAURA DÁNTOLA; LARA REID; JESUÁN J. FARIAS; KARLA P. GARCÍA BELTRÁN; PALOMA LIZONDO; VIRGINIE LHIAUBET-VALLET; VANESA HERLAX; ANDRÉS THOMAS

Lyon

Congreso; 20th Congress of the European Society for photobiology; 2023

Solar radiation causes modifications to different biomolecules and is involved in the generation of human skin cancer. Most of UV solar radiation that reaches the Earth's surface corresponds to UV-A radiation, which can cause damage mainly through photosensitized reactions. Photosensitization consists of the chemical alteration of a compound as a result of the initial absorption of radiation by another chemical species called photosensitzer. At tissue level the photosensitization processes can lead to the generation of neoplasic processes, and the photochemical production of reactive oxygen species (ROS), with the concomitant generation of oxidative stress. These processes are particularly important in individuals with skin diseases that cause alteration in pigmentation, the most protective mechanism against radiation.Due to their relatively high abundance, their ability to bind chromophores, and the reactivity of particular amino acid residues, proteins are one of the preferential targets of the photosensitized damaging effects of UV radiation on biological systems.The oxidation of these biomolecules mediated by radiation may occur via two different pathway: i) direct absorption of radiation by the amino acid residues, ii) absorption of UV-A radiation and/or visible light via endogenous or exogenous photosensitizers, leading to the production of excited species which react with the biomolecule by electron transfer or hydrogen abstraction (Type I mechanism) or energy transfer to molecular oxygen to produce singlet oxygen (1O2,Type II mechanism).1Pterins, a family of heterocyclic compounds, are present in biological systems in multiple forms and play different roles ranging from pigments to enzymatic cofactors for numerous redox and one-carbon transfer reactions. Under pathological conditions, such as vitiligo, oxidized pterins accumulate in the depigmented patches on the skin of patients suffering from this pathology. In aqueous solutions, these molecules are photochemically reactive and, under UV-A excitation, they can fluoresce, produce organic radical and ROS, undergo photooxidation and, photosensitize chemical modification of different biomolecules, such as DNA, proteins and lipids.2In the context of our investigations related to the photosensitizing properties of pterins, this work will show the different modifications that proteins undergo, such as, oligomerization, oxidation, fragmentation and generation of protein-photosensitizer adducts, when these biomolecules are exposed to UV-A radiation in the presence of different pterin derivatives. The reaction mechanisms responsible for these processes, as well as their biological importance, will be analyzed