Methylglyoxal modification enhances the stability of hemoglobin and lowers its iron-mediated oxidation reactions: An in vitro study

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• 作者：Sauradipta Banerjee ; Abhay Sankar Chakraborti ; ^{ascbmbg@caluniv.ac.in} ; ^{abhay_chakraborti@yahoo.co.in}
• 关键词：Hemoglobin ; Methylglyoxal ; Diabetes mellitus ; Advanced glycation end products ; Hydroimidazolone ; Oxidative stress
• 刊名：International Journal of Biological Macromolecules
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：95
• 期：Complete
• 页码：1159-1168
• 全文大小：2256 K
• 卷排序：95

文摘

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. In the present study, we have investigated the in vitro effect of methylglyoxal (200, 300 μm) on the heme protein hemoglobin (HbA0) (100 μm) after incubation for one week at 25 °C. Compared to HbA0, MG-treated HbA0 exhibited decreased absorbance around 280 nm, reduced intrinsic fluorescence and lower surface hydrophobicity. MG treatment was not found to significantly affect the secondary structure of HbA0. The stability of MG-treated HbA0 was found to be higher compared to HbA0. Moreover, H2O2-mediated iron release and subsequent iron-mediated oxidation (Fenton) reactions were found to be lower in presence of MG-treated HbA0 compared to HbA0. As shown by mass spectrometric studies, MG modified Arg-92α, Arg-104β, Arg-31α and Arg-40β of HbA0 to hydroimidazolone adducts. The modifications thus appear to be associated with the observed structural alterations of the heme protein. Considering the increased level of MG in diabetes mellitus as well as its high reactivity, AGEs might be associated with structural and functional modifications of the protein including physiological significance.