Age-associated accumulation of carbamylation-derived products in tissues is independent from the myeloperoxidase pathway in mice.

Date publication

mars 2026

Journal

PloS one

Auteurs

Membres identifiés du Cancéropôle Est :
Pr GILLERY Philippe

Tous les auteurs :
Pietrement C, Okwieka A, Cadoret L, Doué M, Gillery P, Jaisson S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41838640

Résumé

Carbamylation is a nonenzymatic post-translational modification that alters protein structural and functional properties and is involved in the pathogenesis of many diseases. It results from isocyanic acid binding to protein amino groups, generating carbamylation-derived products, including homocitrulline (HCit) when the reaction targets the ε-amino group of lysine residues. Isocyanic acid is produced by two major sources in vivo, the spontaneous dissociation of urea and the myeloperoxidase (MPO)-catalyzed conversion of thiocyanate, but their respective contribution to carbamylation is disputed in literature. Here, we compared tissue accumulation of HCit in wild-type versus MPO-deficient mice during ageing. Our results showed that the kinetics and amplitude of carbamylation were not reduced in MPO-deficient mice. Furthermore, carbamylation was intriguingly enhanced in younger MPO-deficient mice, suggesting the presence of compensatory mechanisms. These findings suggest that the MPO pathway is not necessarily required for age-associated systemic carbamylation.

Mots clés

Animals, Peroxidase, metabolism, Mice, Aging, metabolism, Protein Carbamylation, Citrulline, analogs & derivatives, Mice, Knockout, Protein Processing, Post-Translational, Mice, Inbred C57BL

Référence

PLoS One. 2026 03 16;21(3):e0344708