Changes Due to Ageing in the Glycan Structure of Alpha-2-Macroglobulin and Its Reactivity with Ligands

Abstract

Alpha-2-macroglobulin (α2M) is a molecule generally associated with inflammation, and chronic inflammation is associated with ageing and cancer. The degree of inflammation was recently proposed to be considered as a biomarker of biological ageing. In this study, glycans attached to α2M were analysed in a human population of different ages by lectin-based protein microarray. Higher reactivity of α2M with several lectins was detected in older individuals indicating an increased content of specific monosaccharides: α2,6 sialic acid, mannose and N-acetylglucosamine, and multiantennary complex type N-glycans. The increased glycosylation of α2M was accompanied by reduced binding of Zn ions and insulin-like growth factor-binding protein 2 (IGFBP-2). Glycosylation of α2M and its reactivity with IGFBP-2 is similarly affected by ageing and incidence of colon cancer, but the reactivity of α2M with Zn ions is differently affected, as the binding of Zn ions remains unaltered in patients with colon cancer compared to healthy middle-aged individuals. Thus, the binding of IGFBP-2 to α2M seems to be related to structural changes in the glycan moieties of α2M, whereas binding of Zn ions, most likely, is not.

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Abbreviations

α2M:

Alpha-2-macroglobulin

IGFBP-2:

Insulin-like growth factor-binding protein-2

SNA:

Sambucus nigra agglutinin

ConA:

Concanavalin A

MAL-II:

Maackia amurensis lectin-II

PHA-E:

Phaseolus vulgaris erythroagglutinin

WGA:

Wheat germ agglutinin

LCA:

Lens culinaris agglutinin

AAL:

Aleuria aurantia lectin

RCA-I:

Ricinus communis-I

LBPM:

Lectin-based protein microarray

IMAC:

Immobilised metal-affinity chromatography

DU:

Densitometric unit

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Acknowledgements

This work was supported by the bilateral cooperation Grants (451-03-545/2015-09/01, SK-SRB-2016-0023), APVV SK-SRB-2013-0028 and APVV SK-SRB-2016-0023, and by national Grant Nos. 173042 (Ministry of Education, Science and Technological Development of the Republic of Serbia), VEGA 2/0162/14 and APVV-14-0753. The authors would like to thank Dr Judith Anna Nikolić, a native English speaker for language corrections.

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Correspondence to Miloš Šunderić.

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Šunderić, M., Križáková, M., Malenković, V. et al. Changes Due to Ageing in the Glycan Structure of Alpha-2-Macroglobulin and Its Reactivity with Ligands. Protein J 38, 23–29 (2019). https://doi.org/10.1007/s10930-018-9806-6

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Keywords

  • α2M
  • Age
  • Glycosylation
  • Ligand binding
  • Cancer