The effect of oxygen radicals metabolites and vitamin E on glycosylation of proteins.
Glycosylation (glycation) of proteins is a major complication of hyperglycemia in diabetes. This study has examined the effect of hydrogen peroxide (H2O2) and tertiary-butylhydroperoxide (TBH) and vitamin E (E) on glycation of hemoglobin (GHb). The RBC (15%) in phosphate-buffered saline were treated with 5-50 mM glucose (G) with and without H2O2 or TBH at 37 degrees C for 1-3 d. Glycation of hemoglobin was assessed by GHb formation using Glyc-affinity columns. There was an increase in the GHb formation with increasing G concentrations. GHb formation increased significantly in the presence of H2O2 at all G concentrations. The increase in GHb was blocked when RBC were pretreated with E. E also inhibited formation of malondialdehyde (MDA), an end product of lipid peroxidation, as assessed by the thiobarbituric acid reactivity. Similar increase in the GHb formation was observed when TBH was used instead of H2O2 to induce oxidant stress to the RBC. To examine any role of MDA per se in increased glycation, RBC were treated ex vivo with and without exogenous standard MDA. GHb formation was significantly higher with G-MDA in contrast to G alone. Thus, increased oxygen radicals activity can initiate per-oxidation of lipids and MDA accumulation, which in turn, can stimulate glycation of proteins in diabetes. E can block the glycation of proteins by inhibiting MDA formation.
Jain
S K
SK
Department of Pediatrics, Louisiana State University School of Medicine, Shreveport 71130, USA.
Palmer
M
M
D003920:Diabetes Mellitus / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D006031:Glycosylation / Q000187:drug effects; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D010545:Peroxides / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D005609:Free Radicals; D006442:Glycated Hemoglobin; D006454:Hemoglobins; D006861:Hydrogen Peroxide; D008315:Malondialdehyde; D010545:Peroxides; D011506:Proteins; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D014810:Vitamin E; D020122:tert-Butylhydroperoxide