Structural and functional changes in the insulin molecule produced by oxidative stress.
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.
Medina-Navarro
Rafael
R
Laboratorio de Metabolismo Experimental, Centro de Investigación Biomédica de Michoacán, (CIBIMI-IMSS), Michoacán, México. rafael.medina@imss.gob.mx
Guzmán-Grenfell
Alberto M
AM
Olivares-Corichi
Ivonne
I
Hicks
Juan J
JJ
D041721:3T3-L1 Cells; D000171:Acrolein / Q000494:pharmacology; D000818:Animals; D050260:Carbohydrate Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D017665:Hydroxyl Radical / Q000494:pharmacology; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats
D007328:Insulin; D017665:Hydroxyl Radical; D000171:Acrolein; D005947:Glucose