title: Mechanistic insights in glycation-induced protein aggregation.
abstract: Protein glycation causes loss-of-function through a process that has been associated with several diabetic-related diseases. Additionally, glycation has been hypothesized as a promoter of protein aggregation, which could explain the observed link between hyperglycaemia and the development of several aggregating diseases. Despite its relevance in a range of diseases, the mechanism through which glycation induces aggregation remains unknown. Here we describe the molecular basis of how glycation is linked to aggregation by applying a variety of complementary techniques to study the nonenzymatic glycation of hen lysozyme with ribose (ribosylation) as the reducing carbohydrate. Ribosylation involves a chemical multistep conversion that induces chemical modifications on lysine side chains without altering the protein structure, but changing the protein charge and enlarging its hydrophobic surface. These features trigger lysozyme native-like aggregation by forming small oligomers that evolve into bigger insoluble particles. Moreover, lysozyme incubated with ribose reduces the viability of SH-SY5Y neuroblastoma cells. Our new insights contribute toward a better understanding of the link between glycation and aggregation.
authors: Institut Universitari d'Investigació en Ciències de la Salut (IUNICS), Departament de Química, Universitat de les Illes Balears , Carretera de Valldemossa km 7.5, E-07122 Palma de Mallorca, Spain.
authors: Miquel
authors: M
authors: Adrover
authors: Laura
authors: L
authors: Mariño
authors: Pilar
authors: P
authors: Sanchis
authors: Kris
authors: K
authors: Pauwels
authors: Yvonne
authors: Y
authors: Kraan
authors: Pierre
authors: P
authors: Lebrun
authors: Bartolomé
authors: B
authors: Vilanova
authors: Francisco
authors: F
authors: Muñoz
authors: Kerensa
authors: K
authors: Broersen
authors: Josefa
authors: J
authors: Donoso
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D006031:Glycosylation; D006801:Humans; D009113:Muramidase / Q000737:chemistry* / Q000494:pharmacology; D066329:Protein Aggregates; D012266:Ribose / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D066329:Protein Aggregates; D012266:Ribose; D009113:Muramidase