Mechanistic insights in glycation-induced protein aggregation

M. Adrover, L. Marino, P. Sanchis, K. Pauwels, Yvonne M. Kraan, P. Lebrun, B. Vilanova, F. Munoz, Kerensa Broersen, J. Donoso

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Scopus)

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.
Original languageUndefined
Pages (from-to)3449-3462
Number of pages14
JournalBiomacromolecules
Volume15
Issue number9
DOIs
Publication statusPublished - 2014

Keywords

  • IR-94940
  • METIS-306229

Cite this

Adrover, M., Marino, L., Sanchis, P., Pauwels, K., Kraan, Y. M., Lebrun, P., ... Donoso, J. (2014). Mechanistic insights in glycation-induced protein aggregation. Biomacromolecules, 15(9), 3449-3462. https://doi.org/10.1021/bm501077j
Adrover, M. ; Marino, L. ; Sanchis, P. ; Pauwels, K. ; Kraan, Yvonne M. ; Lebrun, P. ; Vilanova, B. ; Munoz, F. ; Broersen, Kerensa ; Donoso, J. / Mechanistic insights in glycation-induced protein aggregation. In: Biomacromolecules. 2014 ; Vol. 15, No. 9. pp. 3449-3462.
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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.",
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Adrover, M, Marino, L, Sanchis, P, Pauwels, K, Kraan, YM, Lebrun, P, Vilanova, B, Munoz, F, Broersen, K & Donoso, J 2014, 'Mechanistic insights in glycation-induced protein aggregation', Biomacromolecules, vol. 15, no. 9, pp. 3449-3462. https://doi.org/10.1021/bm501077j

Mechanistic insights in glycation-induced protein aggregation. / Adrover, M.; Marino, L.; Sanchis, P.; Pauwels, K.; Kraan, Yvonne M.; Lebrun, P.; Vilanova, B.; Munoz, F.; Broersen, Kerensa; Donoso, J.

In: Biomacromolecules, Vol. 15, No. 9, 2014, p. 3449-3462.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Mechanistic insights in glycation-induced protein aggregation

AU - Adrover, M.

AU - Marino, L.

AU - Sanchis, P.

AU - Pauwels, K.

AU - Kraan, Yvonne M.

AU - Lebrun, P.

AU - Vilanova, B.

AU - Munoz, F.

AU - Broersen, Kerensa

AU - Donoso, J.

PY - 2014

Y1 - 2014

N2 - 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.

AB - 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.

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Adrover M, Marino L, Sanchis P, Pauwels K, Kraan YM, Lebrun P et al. Mechanistic insights in glycation-induced protein aggregation. Biomacromolecules. 2014;15(9):3449-3462. https://doi.org/10.1021/bm501077j