Protective effect of extractive and biotechnological chondroitin in insulin amyloid and advanced glycation end product-induced toxicity

J Cell Physiol. 2019 Apr;234(4):3814-3828. doi: 10.1002/jcp.27153. Epub 2018 Sep 7.

Abstract

Glycosaminoglycans are extracellular matrix components related to several biological functions and diseases. Chondroitin sulfate is a sulphated glycosaminoglycan synthesized as part of proteoglycan molecules. They are frequently associated with amyloid deposits and possess an active role in amyloid fibril formation. Recently, a neuroprotective effect of extracellular matrix components against amyloid toxicity and oxidative stress has been reported. Advanced glycation end products (AGEs), the end products of the glycation reaction, have been linked to amyloid-based neurodegenerative disease as associated with oxidative stress and inflammation. In this study we have analyzed the effect of chondroitin sulfate isolated from different species, in comparison with a new biotechnological unsulfated chondroitin, in the amyloid aggregation process of insulin, as well as the ability to prevent the formation of AGEs and related toxicity. The results have showed a determining role of chondroitin sulfate groups in modulating insulin amyloid aggregation. In addition, both sulfated and unsulfated chondroitins have shown protective properties against amyloid and AGEs-induced toxicity. These data are very relevant as a protective effect of these glycosaminoglycans in the AGE-induced toxicity was never observed before. Moreover, considering the issues related to the purity and safety of chondroitin from natural sources, this study suggests a new potential application for the biotechnological chondroitin.

Keywords: AGEs; amyloid aggregation; cell toxicity; chondroitin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / toxicity*
  • Animals
  • Cattle
  • Cell Line, Tumor
  • Chondroitin Sulfates / isolation & purification
  • Chondroitin Sulfates / pharmacology*
  • Cytoprotection
  • Diabetic Neuropathies / metabolism
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / prevention & control*
  • Glycation End Products, Advanced / toxicity*
  • Humans
  • Insulin / toxicity*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Neuroprotective Agents / pharmacology*
  • Protein Aggregates
  • Protein Aggregation, Pathological
  • Protein Binding
  • Reactive Oxygen Species / metabolism
  • Sharks
  • Sus scrofa

Substances

  • Amyloid
  • Glycation End Products, Advanced
  • Insulin
  • Neuroprotective Agents
  • Protein Aggregates
  • Reactive Oxygen Species
  • Chondroitin Sulfates