title: Glyoxal administration induces formation of high molecular weight aggregates of hemoglobin exhibiting amyloidal nature in experimental rats: An in vivo study.
abstract: Glyoxal, a highly reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs). In the present study, we have investigated the effect of glyoxal on experimental rat hemoglobin in vivo after external administration of the α-dicarbonyl compound in animals. Gel electrophoretic profile of hemolysate collected from glyoxal-treated rats (32mg/kg body wt. dose) after one week exhibited the presence of some high molecular weight protein bands that were found to be absent for control, untreated rats. Mass spectrometric and absorption studies indicated that the bands represented hemoglobin. Further studies revealed that the fraction exhibited the presence of intermolecular cross β-sheet structure. Thus glyoxal administration induces formation of high molecular weight aggregates of hemoglobin with amyloid characteristics in rats. Aggregated hemoglobin fraction was found to exhibit higher stability compared to glyoxal-untreated hemoglobin. As evident from mass spectrometric studies, glyoxal was found to modify Arg-30β and Arg-31α of rat hemoglobin to hydroimidazolone adducts. The modifications thus appear to induce amyloid-like aggregation of hemoglobin in rats. Considering the increased level of glyoxal in diabetes mellitus as well as its high reactivity, the above findings may be physiologically significant.
authors.affiliation: Department of Biophysics, Molecular Biology & Bioinformatics, University of Calcutta, 92, Acharyya Prafulla Chandra Road, Kolkata 700009, India. Electronic address: ascbmbg@caluniv.ac.in.
authors.forename: Sauradipta
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Department of Biophysics, Molecular Biology & Bioinformatics, University of Calcutta, 92, Acharyya Prafulla Chandra Road, Kolkata 700009, India. Electronic address: abhay_chakraborti@yahoo.co.in.
authors.forename: Abhay Sankar
authors.initials: AS
authors.lastname: Chakraborti
mesh_terms: D000682:Amyloid / Q000097:blood*; D000818:Animals; D006037:Glyoxal / Q000633:toxicity*; D006454:Hemoglobins / Q000378:metabolism*; D008297:Male; D066263:Protein Aggregation, Pathological / Q000097:blood* / Q000139:chemically induced*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000682:Amyloid; D006454:Hemoglobins; D006037:Glyoxal
keywords: Advanced glycation end products; Amyloid-like aggregation; Glyoxal; Hemoglobin; Hydroimidazolone; Mass spectrometry