Oxidative modification of skin collagen

Oxidative modification of collagen contributes to the loss of skin structure and function during aging and disease. Although reactive oxygen species are known to damage collagen, the radical intermediates and fragmentation mechanism responsible for collagen degradation remain poorly understood. In this study, we investigated whether azocompound-derived peroxyl radicals induce collagen fragmentation through the formation of protein radicals (carbon-centered) and alkoxyl radicals (oxygen-centered) in skin tissue. Using EPR spectroscopy, fluorescence analysis, immunoblotting, and LC-MS/MS profiling, we demonstrated that hydrogen abstraction from collagen generates protein radicals, which are subsequently converted to alkoxyl radicals. We further show that these alkoxyl radicals may undergo β-scission, leading to cleavage between the α‑carbon of the collagen backbone and the C-3 carbon of the amino acid side chain. This process promotes side-chain detachment and contributes to fragmentation of collagen type I. Because collagen accounts for approximately 75% of the dry weight of skin and type I collagen represents 80-90% of total dermal collagen, oxidative fragmentation of collagen may substantially impair skin integrity and contribute to skin aging as well as to pathological tissue remodeling associated with fibrotic, autoimmune, and skin neoplastic diseases.