Protein carbamylation: hallmark of ageing
Philippe Gillery
Laboratory of Medical Biochemistry and Molecular Biology, UMR CNRS/URCA n°7369, Faculty of Medicine, Reims, France
Among age-related processes are the chemical reactions referred to as "nonenzymatic post-translational modifications" (NEPTM), which are responsible for protein molecular ageing. Carbamylation is a recently described NEPTM due to the binding of isocyanate, derived from urea dissociation or from myeloperoxidase-mediated catabolism of thiocyanate, to amino groups of proteins. The most characteristic carbamylation-derived product (CDP) is homocitrulline generated from lysine residues. Carbamylation induces adverse alterations of protein structure, functions and interactions with cells.
Clinical studies have shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes. However, nothing was known about tissue protein carbamylation during aging. To address this issue, we have evaluated the evolution of homocitrulline content over time in skin of three mammalian species with different life expectancies. Carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of CPDs, especially in extracellular matrix proteins with long half-life like type I collagen and elastin. The accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. Besides, homocitrulline accumulates in tissues more intensely than carboxymethyl-lysine, one of the major advanced glycation end-product generated by another NEPTM, glycoxidation. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species and may significantly contribute in the structural and functional tissue damages encountered during aging.
Financial interest disclosure: none to declare.
Philippe Gillery
Laboratory of Medical Biochemistry and Molecular Biology, UMR CNRS/URCA n°7369, Faculty of Medicine, Reims, France
Among age-related processes are the chemical reactions referred to as "nonenzymatic post-translational modifications" (NEPTM), which are responsible for protein molecular ageing. Carbamylation is a recently described NEPTM due to the binding of isocyanate, derived from urea dissociation or from myeloperoxidase-mediated catabolism of thiocyanate, to amino groups of proteins. The most characteristic carbamylation-derived product (CDP) is homocitrulline generated from lysine residues. Carbamylation induces adverse alterations of protein structure, functions and interactions with cells.
Clinical studies have shown that carbamylated proteins increase in plasma and tissues during chronic kidney disease and are associated with deleterious clinical outcomes. However, nothing was known about tissue protein carbamylation during aging. To address this issue, we have evaluated the evolution of homocitrulline content over time in skin of three mammalian species with different life expectancies. Carbamylation occurs throughout the whole lifespan and leads to tissue accumulation of CPDs, especially in extracellular matrix proteins with long half-life like type I collagen and elastin. The accumulation rate of CDPs is inversely correlated with longevity, suggesting the occurrence of still unidentified protective mechanisms. Besides, homocitrulline accumulates in tissues more intensely than carboxymethyl-lysine, one of the major advanced glycation end-product generated by another NEPTM, glycoxidation. Thus, protein carbamylation may be considered a hallmark of aging in mammalian species and may significantly contribute in the structural and functional tissue damages encountered during aging.
Financial interest disclosure: none to declare.
