Structural and functional changes in the insulin molecule produced by oxidative stress

Rafael Medina-Navarro, Alberto M. Guzmán-Grenfell, Ivonne Olivares-Corichi, Juan J. Hicks

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

3 Scopus citations

Abstract

The change produced by oxidative stress on proteins (cross-links, backbone cleavage, amino acid modification) generates structural changes with a wide range of consequences such as increased propensity to the aggregation or proteolysis, altered immunogenicity and frequently enzymatic and binding inhibition. Insulin is particularly sensitive to conformational changes, aggregation and cross-linking; any change on insulin could impair its function. We have examined the biological activity of insulin modified by hydroxyl radical and exposed to acrolein in rats and adiposites. We found out important changes that we have shown as prototype of possible effect of oxidative stress on the structural and functional damage to insulin. Whereas, hydroxyl radical and acrolein both have diminished the hypoglycemic effect of insulin in vivo, and the effect of acrolein seems be to involved in carbonylation and not derived from inter-molecular cross-links formation or aggregates. The effect was highly stimulated at alkaline pH, concomitant with carbonyl formation and then probably aldolic condensation type reaction-dependent. Hydroxyls radical generates tyrosine derivative formation and introduces non aldehyde dependent carbonyls in the insulin molecule.

Original languageEnglish
Title of host publicationAdvanced Protocols in Oxidative Stress II
PublisherHumana Press Inc.
Pages141-153
Number of pages13
ISBN (Print)9781607614104
DOIs
StatePublished - 2010

Publication series

NameMethods in Molecular Biology
Volume594
ISSN (Print)1064-3745

Keywords

  • Acrolein
  • Aldehydes
  • Carbonyls
  • Hydroxyl radical
  • Insulin
  • Oxidative stress
  • Protein oxidation
  • Quinones

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