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Protein & Peptide Letters

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ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

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Research Article

Effect of Glyoxal Modification on a Critical Arginine Residue (Arg-31α) of Hemoglobin: Physiological Implications of Advanced Glycated end Product an in vitro Study

Author(s): Sauradipta Banerjee*

Volume 27, Issue 8, 2020

Page: [770 - 781] Pages: 12

DOI: 10.2174/0929866526666191125101122

Price: $65

Abstract

Background: Non-enzymatic protein glycation is involved in structure and stability changes that impair protein functionality, resulting in several human diseases, such as diabetes and amyloidotic neuropathies (Alzheimer’s disease, Parkinson’s disease and Andrade’s syndrome). Glyoxal, an endogenous reactive oxoaldehyde, increases in diabetes and reacts with several proteins to form advanced glycation end products through Maillard-like reaction.

Objective: Human hemoglobin, the most abundant protein in blood cells is subjected to nonenzymatic modification by reactive oxoaldehydes in diabetic condition. In the present study, the effect of a low concentration of glyoxal (5 μM) on hemoglobin (10 μM) has been investigated following a period of 30 days incubation in vitro.

Methods: Different techniques, mostly biophysical and spectroscopic (e.g. circular dichroism, differential scanning calorimetric study, dynamic light scattering, mass spectrometry, etc.) were used to study glyoxal-induced changes of hemoglobin.

Results: Glyoxal-treated hemoglobin exhibits decreased absorbance around 280 nm, decreased fluorescence and reduced surface hydrophobicity compared to normal hemoglobin. Glyoxal treatment enhances the stability of hemoglobin and lowers its susceptibility to thermal aggregation compared to control hemoglobin as seen by different studies. Finally, peptide mass fingerprinting study showed glyoxal to modify an arginine residue of α-chain of hemoglobin (Arg-31α) to hydroimidazolone.

Conclusion: Increased level of glyoxal in diabetes mellitus as well as its high reactivity may cause modifications of the heme protein. Thus, considering the significance of glyoxal-induced protein modification under physiological conditions, the observation appears clinically relevant in terms of understanding hydroimidazolone-mediated protein modification under in vivo conditions.

Keywords: Glyoxal, hemoglobin, advanced glycation end product, hydroimidazolone, mass spectrometry, absorbance.

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[1]
Ahmad, S. Moinuddin; Dixit, K.; Shahab, U.; Alam, K.; Ali, A. Genotoxicity and immunogenicity of DNA-advanced glycation end products formed by methylglyoxal and lysine in presence of Cu2+. Biochem. Biophys. Res. Commun., 2011, 407(3), 568-574.
[http://dx.doi.org/10.1016/j.bbrc.2011.03.064] [PMID: 21420380]
[2]
Ahmad, M.I.; Ahmad, S. Moinuddin, Preferential recognition of methylglyoxal-modified calf thymus DNA by circulating antibodies in cancer patients. Indian J. Biochem. Biophys., 2011, 48(4), 290-296.
[PMID: 22053699]
[3]
Wolffenbuttel, B.H.; Giordano, D.; Founds, H.W.; Bucala, R. Long-term assessment of glucose control by haemoglobin-AGE measurement. Lancet, 1996, 347(9000), 513-515.
[http://dx.doi.org/10.1016/S0140-6736(96)91141-1] [PMID: 8596270]
[4]
Bose, T.; Bhattacherjee, A.; Banerjee, S.; Chakraborti, A.S. Methylglyoxal-induced modifications of hemoglobin: Structural and functional characteristics. Arch. Biochem. Biophys., 2013, 529(2), 99-104.
[http://dx.doi.org/10.1016/j.abb.2012.12.001] [PMID: 23232081]
[5]
Siddiqui, Z.; Ishtikhar, M. Moinuddin; Ahmad, S. d-Ribose induced glycoxidative insult to hemoglobin protein: An approach to spot its structural perturbations. Int. J. Biol. Macromol., 2018, 112, 134-147.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.161] [PMID: 29378270]
[6]
Siddiqui, Z.; Faisal, M.; Alatar, A.A.; Ahmad, S. Glycation of hemoglobin leads to the immunogenicity as a result of neo-epitope generation. Int. J. Biol. Macromol., 2019, 123, 427-435.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.11.063] [PMID: 30445080]
[7]
Bose, T.; Chakraborti, A.S. Fructose-induced structural and functional modifications of hemoglobin: Implication for oxidative stress in diabetes mellitus. Biochim. Biophys. Acta, 2008, 1780(5), 800-808.
[http://dx.doi.org/10.1016/j.bbagen.2008.02.001] [PMID: 18339326]
[8]
Ahmed, N.; Dobler, D.; Dean, M.; Thornalley, P.J. Peptide mapping identifies hotspot site of modification in human serum albumin by methylglyoxal involved in ligand binding and esterase activity. J. Biol. Chem., 2005, 280(7), 5724-5732.
[http://dx.doi.org/10.1074/jbc.M410973200] [PMID: 15557329]
[9]
Kalapos, M.P. Methylglyoxal in living organisms: Chemistry, biochemistry, toxicology and biological implications. Toxicol. Lett., 1999, 110(3), 145-175.
[http://dx.doi.org/10.1016/S0378-4274(99)00160-5] [PMID: 10597025]
[10]
Thornalley, P.J.; Langborg, A.; Minhas, H.S. Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem. J., 1999, 344(Pt 1), 109-116.
[http://dx.doi.org/10.1042/bj3440109] [PMID: 10548540]
[11]
Fu, M.; Requena, J.R.; Jenkins, A.J.; Lyons, T.J.; Baynes, J.W.; Thorpe, S.R. The advanced glycation end product, Nε-(carboxymethyl) lysine, is a product of both lipid peroxidation and glycoxidation reactions. J. Biol. Chem., 1996, 271(17), 9982-9986.
[http://dx.doi.org/10.1074/jbc.271.17.9982] [PMID: 8626637]
[12]
Anderson, M.M.; Hazen, S.L.; Hsu, F.F.; Heinecke, J.W. Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxy-amino acids into glycolaldehyde, 2-hydroxypropanal, and acrolein. A mechanism for the generation of highly reactive α-hydroxy and α,β-unsaturated aldehydes by phagocytes at sites of inflammation. J. Clin. Invest., 1997, 99(3), 424-432.
[http://dx.doi.org/10.1172/JCI119176] [PMID: 9022075]
[13]
Lapolla, A.; Flamini, R.; Dalla Vedova, A.; Senesi, A.; Reitano, R.; Fedele, D.; Basso, E.; Seraglia, R.; Traldi, P. Glyoxal and methylglyoxal levels in diabetic patients: Quantitative determination by a new GC/MS method. Clin. Chem. Lab. Med., 2003, 41(9), 1166-1173.
[http://dx.doi.org/10.1515/CCLM.2003.180] [PMID: 14598866]
[14]
Kumar, M.S.; Reddy, P.Y.; Kumar, P.A.; Surolia, I.; Reddy, G.B. Effect of dicarbonyl-induced browning on α-crystallin chaperone-like activity: Physiological significance and caveats of in vitro aggregation assays. Biochem. J., 2004, 379(Pt 2), 273-282.
[http://dx.doi.org/10.1042/bj20031633] [PMID: 14711370]
[15]
Mikulíková, K.; Miksík, I.; Deyl, Z. Non-enzymatic posttranslational modifications of bovine serum albumin by oxo-compounds investigated by chromatographic and electrophoretic methods. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2005, 815(1-2), 315-331.
[http://dx.doi.org/10.1016/j.jchromb.2004.10.062] [PMID: 15652820]
[16]
Banerjee, S. Formation of pentosidine cross-linking in myoglobin by glyoxal: Detection of fluorescent advanced glycation end product. J. Fluoresc., 2017, 27(4), 1213-1219.
[http://dx.doi.org/10.1007/s10895-017-2064-8] [PMID: 28299531]
[17]
Chen, H.C.; Liu, C.T.; Li, Y.J. Correlation between glyoxal-induced DNA cross-links and hemoglobin modifications in human blood measured by mass spectrometry. Chem. Res. Toxicol., 2018, 32(1), 179-189.
[http://dx.doi.org/10.1021/acs.chemrestox.8b00264] [PMID: 30507124]
[18]
Banerjee, S.; Chakraborti, A.S. Glyoxal administration induces formation of high molecular weight aggregates of hemoglobin exhibiting amyloidal nature in experimental rats: An in vivo study. Int. J. Biol. Macromol., 2016, 93(Pt A), 805-813.
[http://dx.doi.org/10.1016/j.ijbiomac.2016.09.061] [PMID: 27645921]
[19]
Ahmed, M.U.; Thorpe, S.R.; Baynes, J.W. Identification of N ε-carboxymethyllysine as a degradation product of fructoselysine in glycated protein. J. Biol. Chem., 1986, 261(11), 4889-4894.
[PMID: 3082871]
[20]
Iijima, K.; Murata, M.; Takahara, H.; Irie, S.; Fujimoto, D. Identification of N(ω)-carboxymethylarginine as a novel acid-labileadvanced glycation end product in collagen. Biochem. J., 2000, 347(Pt 1), 23-27.
[http://dx.doi.org/10.1042/bj3470023] [PMID: 10727397]
[21]
Banerjee, S.; Chakraborti, A.S. Structural alterations of hemoglobin and myoglobin by glyoxal: A comparative study. Int. J. Biol. Macromol., 2014, 66, 311-318.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.02.034] [PMID: 24613676]
[22]
Banerjee, S. Glyoxal-induced modification enhances stability of hemoglobin and lowers iron-mediated oxidation reactions of the heme protein: An in vitro study. (Int. J. Biol. Macromol.)2018, 107(Pt A), 494-501.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.08.180] [PMID: 28888546]
[23]
Cohen, M.P.; Wu, V.Y. Purification of glycated hemoglobin. Methods Enzymol., 1994, 231, 65-75.
[http://dx.doi.org/10.1016/0076-6879(94)31007-6] [PMID: 8041283]
[24]
Bhattacharyya, J.; Bhattacharyya, M.; Chakrabarty, A.S.; Chaudhuri, U.; Poddar, R.K. Interaction of chlorpromazine with myoglobin and hemoglobin. A comparative study. Biochem. Pharmacol., 1994, 47(11), 2049-2053.
[http://dx.doi.org/10.1016/0006-2952(94)90080-9] [PMID: 8010989]
[25]
Satish Kumar, M.; Mrudula, T.; Mitra, N.; Bhanuprakash Reddy, G. Enhanced degradation and decreased stability of eye lens α-crystallin upon methylglyoxal modification. Exp. Eye Res., 2004, 79(4), 577-583.
[http://dx.doi.org/10.1016/j.exer.2004.07.003] [PMID: 15381041]
[26]
Chen, Y.H.; Yang, J.T.; Martinez, H.M. Determination of the secondary structures of proteins by circular dichroism and optical rotatory dispersion. Biochemistry, 1972, 11(22), 4120-4131.
[http://dx.doi.org/10.1021/bi00772a015] [PMID: 4343790]
[27]
Navarra, G.; Giacomazza, D.; Leone, M.; Librizzi, F.; Militello, V.; San Biagio, P.L. Thermal aggregation and ion-induced cold-gelation of bovine serum albumin. Eur. Biophys. J., 2009, 38(4), 437-446.
[http://dx.doi.org/10.1007/s00249-008-0389-6] [PMID: 19132367]
[28]
Bismuto, E.; Gratton, E.; Lamb, D.C. Dynamics of ANS binding to tuna apomyoglobin measured with fluorescence correlation spectroscopy. Biophys. J., 2001, 81(6), 3510-3521.
[http://dx.doi.org/10.1016/S0006-3495(01)75982-6] [PMID: 11721012]
[29]
Del Vecchio, P.; Graziano, G.; Granata, V.; Barone, G.; Mandrich, L.; Rossi, M.; Manco, G. Denaturing action of urea and guanidine hydrochloride towards two thermophilic esterases. Biochem. J., 2002, 367(Pt 3), 857-863.
[http://dx.doi.org/10.1042/bj20020695] [PMID: 12160466]
[30]
Chen, Y.H.; He, R.Q.; Liu, Y.; Liu, Y.; Xue, Z.G. Effect of human neuronal tau on denaturation and reactivation of rabbit muscle D-glyceraldehyde-3-phosphate dehydrogenase. Biochem. J., 2000, 351(Pt 1), 233-240.
[http://dx.doi.org/10.1042/bj3510233] [PMID: 10998366]
[31]
GhoshMoulick,. R.; Bhattacharya, J.; Roy, S.; Basak, S.; Dasgupta, A.K. Compensatory secondary structural alterations in protein glycation. Biochim. Biophys. Acta, 2007, 1774(2), 233-242.
[http://dx.doi.org/10.1016/j.bbapap.2006.11.018] [PMID: 17234463]
[32]
Borana, M.S.; Mishra, P.; Pissurlenkar, R.R.S.; Hosur, R.V.; Ahmad, B. Curcumin and kaempferol prevent lysozyme fibril formation by modulating aggregation kinetic parameters. Biochim. Biophys. Acta, 2014, 1844(3), 670-680.
[http://dx.doi.org/10.1016/j.bbapap.2014.01.009] [PMID: 24468532]
[33]
Banerjee, S.; Maity, S.; Chakraborti, A.S. Methylglyoxal-induced modification causes aggregation of myoglobin. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2016, 155, 1-10.
[http://dx.doi.org/10.1016/j.saa.2015.10.022] [PMID: 26554310]
[34]
Iram, A.; Naeem, A. Detection and analysis of protofibrils and fibrils of hemoglobin: Implications for the pathogenesis and cure of heme loss related maladies. Arch. Biochem. Biophys., 2013, 533(1-2), 69-78.
[http://dx.doi.org/10.1016/j.abb.2013.02.019] [PMID: 23500139]
[35]
Iram, A.; Alam, T.; Khan, J.M.; Khan, T.A.; Khan, R.H.; Naeem, A. Molten globule of hemoglobin proceeds into aggregates and advanced glycated end products. PLoS One, 2013, 8(8)e72075
[http://dx.doi.org/10.1371/journal.pone.0072075] [PMID: 23991043]
[36]
Kang, J.H. Oxidative modification of human ceruloplasmin by methylglyoxal: An in vitro study. J. Biochem. Mol. Biol., 2006, 39(3), 335-338.
[PMID: 16756764]
[37]
Chattopadhyay, K.; Mazumdar, S. Structural and conformational stability of horseradish peroxidase: Effect of temperature and pH. Biochemistry, 2000, 39(1), 263-270.
[http://dx.doi.org/10.1021/bi990729o] [PMID: 10625502]
[38]
Carvalho, A.S.L.; Melo, E.P.; Ferreira, B.S.; Neves-Petersen, M.T.; Petersen, S.B.; Aires-Barros, M.R. Heme and pH-dependent stability of an anionic horseradish peroxidase. Arch. Biochem. Biophys., 2003, 415(2), 257-267.
[http://dx.doi.org/10.1016/S0003-9861(03)00275-3] [PMID: 12831850]
[39]
Rondeau, P.; Navarra, G.; Cacciabaudo, F.; Leone, M.; Bourdon, E.; Militello, V. Thermal aggregation of glycated bovine serum albumin. Biochim. Biophys. Acta, 2010, 1804(4), 789-798.
[http://dx.doi.org/10.1016/j.bbapap.2009.12.003] [PMID: 20006741]
[40]
Pham, V.T.; Ewing, E.; Kaplan, H.; Choma, C.; Hefford, M.A. Glycation improves the thermostability of trypsin and chymotrypsin. Biotechnol. Bioeng., 2008, 101(3), 452-459.
[http://dx.doi.org/10.1002/bit.21919] [PMID: 18470893]
[41]
Gangadhariah, M.H.; Wang, B.; Linetsky, M.; Henning, C.; Spanneberg, R.; Glomb, M.A.; Nagaraj, R.H. Hydroimidazolone modification of human alphaA-crystallin: Effect on the chaperone function and protein refolding ability. Biochim. Biophys. Acta, 2010, 1802(4), 432-441.
[http://dx.doi.org/10.1016/j.bbadis.2010.01.010] [PMID: 20085807]
[42]
Nagaraj, R.H.; Panda, A.K.; Shanthakumar, S.; Santhoshkumar, P.; Pasupuleti, N.; Wang, B.; Biswas, A. Hydroimidazolone modification of the conserved Arg12 in small heat shock proteins: Studies on the structure and chaperone function using mutant mimics. PLoS One, 2012, 7(1)e30257
[http://dx.doi.org/10.1371/journal.pone.0030257] [PMID: 22272318]
[43]
Gomes, R.A.; Oliveira, L.M.; Silva, M.; Ascenso, C.; Quintas, A.; Costa, G.; Coelho, A.V.; Sousa Silva, M.; Ferreira, A.E.; Freire, A.P.; Cordeiro, C. Protein glycation in vivo: Functional and structural effects on yeast enolase. Biochem. J., 2008, 416(3), 317-326.
[http://dx.doi.org/10.1042/BJ20080632] [PMID: 18651835]
[44]
Luthra, M.; Balasubramanian, D. Non-enzymatic glycation alters protein structure and stability. J. Biol. Chem., 1993, 268, 18119-18127.
[PMID: 8349689]
[45]
Biswas, A.; Wang, B.; Miyagi, M.; Nagaraj, R.H. Effect of methylglyoxal modification on stress-induced aggregation of client proteins and their chaperoning by human alphaA-crystallin. Biochem. J., 2008, 409(3), 771-777.
[http://dx.doi.org/10.1042/BJ20071006] [PMID: 17941823]
[46]
Gao, Y.; Wang, Y. Site-selective modifications of arginine residues in human hemoglobin induced by methylglyoxal. Biochemistry, 2006, 45(51), 15654-15660.
[http://dx.doi.org/10.1021/bi061410o] [PMID: 17176087]
[47]
Gomes, R.A.; Vicente Miranda, H.; Silva, M.S.; Graça, G.; Coelho, A.V.; Ferreira, A.E.; Cordeiro, C.; Freire, A.P. Yeast protein glycation in vivo by methylglyoxal. Molecular modification of glycolytic enzymes and heat shock proteins. FEBS J., 2006, 273(23), 5273-5287.
[http://dx.doi.org/10.1111/j.1742-4658.2006.05520.x] [PMID: 17064314]
[48]
Lebioda, L.; Stec, B.; Brewer, J.M. The structure of yeast enolase at 2.25-A resolution. An 8-fold beta + alpha-barrel with a novel beta beta alpha alpha (beta alpha)6 topology. J. Biol. Chem., 1989, 264(7), 3685-3693.
[PMID: 2645275]
[49]
Bhattacherjee, A.; Chakraborti, A.S. Fructose-induced modifications of myoglobin: Change of structure from met (Fe3+) to oxy (Fe2+) form. Int. J. Biol. Macromol., 2011, 48(1), 202-209.
[http://dx.doi.org/10.1016/j.ijbiomac.2010.11.003] [PMID: 21087622]
[50]
Sreejayan, N.; Yang, X.; Palanichamy, K.; Dolence, K.; Ren, J. Antioxidant properties of argpyrimidine. Eur. J. Pharmacol., 2008, 593(1-3), 30-35.
[http://dx.doi.org/10.1016/j.ejphar.2008.07.030] [PMID: 18692042]
[51]
Puttaiah, S.; Biswas, A.; Staniszewska, M.; Nagaraj, R.H. Methylglyoxal inhibits glycation-mediated loss in chaperone function and synthesis of pentosidine in α-crystallin. Exp. Eye Res., 2007, 84(5), 914-921.
[http://dx.doi.org/10.1016/j.exer.2007.01.013] [PMID: 17368444]

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