Methylglyoxal-induced modification causes aggregation of myoglobin

• Published in: Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy Vol. 155; pp. 1 - 10
• Main Authors: Banerjee, Sauradipta, Maity, Subhajit, Chakraborti, Abhay Sankar
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 15.02.2016
• Subjects: Advanced glycation end products; Amino Acid Sequence; Amyloid structure; Animals; Glycation End Products, Advanced - metabolism; Horses; Methylglyoxal; Molecular Sequence Data; Myoglobin; Myoglobin - chemistry; Myoglobin - metabolism; Myoglobin - ultrastructure; Protein Aggregates; Protein aggregation; Protein Conformation; Pyruvaldehyde - metabolism; Myoglobin; Methylglyoxal; Advanced glycation end products; Protein aggregation; Amyloid structure
• ISSN: 1386-1425; 1873-3557
• DOI: 10.1016/j.saa.2015.10.022

Post-translational modification of proteins by Maillard reaction, known as glycation, is thought to be the root cause of different complications, particularly in diabetes mellitus and age-related disorders. Methylglyoxal (MG), a reactive α-oxoaldehyde, increases in diabetic condition and reacts with proteins to form advanced glycation end products (AGEs) following Maillard-like reaction. We have investigated the in vitro effect of MG (200μM) on the monomeric heme protein myoglobin (Mb) (100μM) in a time-dependent manner (7 to 18days incubation at 25°C). MG induces significant structural alterations of the heme protein, including heme loss, changes in tryptophan fluorescence, decrease of α-helicity with increased β-sheet content etc. These changes occur gradually with increased period of incubation. Incubation of Mb with MG for 7days results in formation of the AGE adducts: carboxyethyllysine at Lys-16, carboxymethyllysine at Lys-87 and carboxyethyllysine or pyrraline-carboxymethyllysine at Lys-133. On increasing the period of incubation up to 14days, additional AGEs namely, carboxyethyllysine at Lys-42 and hydroimidazolone or argpyrimidine at Arg-31 and Arg-139 have been detected. MG also induces aggregation of Mb, which is clearly evident with longer period of incubation (18days), and appears to have amyloid nature. MG-derived AGEs may thus have an important role as the precursors of protein aggregation, which, in turn, may be associated with physiological complications. [Display omitted] •Methylglyoxal (MG) interacts with myoglobin (Mb) by Maillard reaction.•MG modifies several lysine and arginine residues of Mb in a time-dependent manner.•MG-derived advanced glycation end products induce structural alterations of Mb.•MG-modification leads to amyloid-like aggregation of Mb at longer incubation time.