Physico-chemical Changes Induced in the Serum Proteins Immunoglobulin G and Fibrinogen Mediated by Methylglyoxal

Author(s): Shahnawaz Rehman, Mohammad Faisal, Abdulrahman A. Alatar, Saheem Ahmad*

Journal Name: Current Protein & Peptide Science

Volume 21 , Issue 9 , 2020


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Graphical Abstract:


Abstract:

Background: Non-enzymatic glycation of proteins plays a significant role in the pathogenesis of secondary diabetic complications via the formation of advanced glycation end products (AGEs) and increased oxidative stress. Methylglyoxal (MG), a highly reactive dicarbonyl of class α-oxoaldehyde that generates during glucose oxidation and lipid peroxidation, contributes to glycation.

Objective: This comparative study focuses on methylglyoxal induced glycoxidative damage suffered by immunoglobulin G (IgG) and fibrinogen, and to unveil implication of structural modification of serum proteins in diabetes-associated secondary complications.

Methods: The methylglyoxal induced structural alterations in IgG and fibrinogen were analyzed by UVvis, fluorescence, circular dichroism and Fourier transform infrared (FT-IR) spectroscopy. Ketoamine moieties, carbonyl contents, 5-Hydroxymethylfurfural (HMF) and malondyaldehyde were also quantified. Free lysine and arginine estimation, detection of non-fluorogenic carboxymethyllysine (CML) and fibril formation were confirmed by thioflavin T (ThT) assay.

Results: Structural alterations, increased carbonyl contents and ketoamines were reported in MG glycated IgG and fibrinogen against their native analogues.

Conclusion: The experiment results validate structural modifications, increased oxidative stress and AGEs formation. Thus, we can conclude that IgG-AGEs and Fib-AGEs formed during MG induced glycation of IgG and fibrinogen could impede normal physiology and might initiates secondary complications in diabetic patients.

Keywords: Glycation, immunoglobulin G, fibrinogen, methylglyoxal (MG), advanced glycation end products (AGEs), serum proteins.

[1]
Ahmad, S.; Khan, H.; Siddiqui, Z.; Khan, M.Y.; Rehman, S.; Shahab, U.; Godovikova, T.; Silnikov, V. AGEs, RAGEs and s-RAGE; friend or foe for cancer. Semin. Cancer Biol., 2018, 49, 44-55.
[http://dx.doi.org/10.1016/j.semcancer.2017.07.001 ] [PMID: 28712719]
[2]
Ahmad, S.; Akhter, F.; Shahab, U.; Khan, M.S. Studies on glycation of human low density lipoprotein: a functional insight into physico-chemical analysis. IJBM, 2013, 62, 167-171.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.08.037 ] [PMID: 24012841]
[3]
Rodnick, K.J.; Holman, R.W.; Ropski, P.S.; Huang, M.; Swislocki, A.L. A Perspective on Reagent diversity and non-covalent binding of reactive carbonyl species (RCS) and effector reagents in non-enzymatic glycation (NEG): Mechanistic considerations and implications for future research. Front Chem., 2017, 5, 39.
[http://dx.doi.org/10.3389/fchem.2017.00039]
[4]
Brings, S.; Fleming, T.; Freichel, M.; Muckenthaler, M.U.; Herzig, S.; Nawroth, P.P. Dicarbonyls and advanced glycation end-products in the development of diabetic complications and targets for intervention. Int. J. Mol. Sci., 2017, 18(5), 984.
[http://dx.doi.org/10.3390/ijms18050984] [PMID: 28475116]
[5]
Lee, C.; Park, C. Bacterial responses to glyoxal and methylglyoxal: reactive electrophilic species. Int. J. Mol. Sci., 2017, 18(1), 169.
[http://dx.doi.org/10.3390/ijms18010169 ] [PMID: 28106725 ]
[6]
Allaman, I.; Bélanger, M.; Magistretti, P.J. Methylglyoxal, the dark side of glycolysis. Front. Neurol., 2015, 9, 23.
[http://dx.doi.org/10.3389/fnins.2015.00023] [PMID: 25709564 ]
[7]
Bohlender, J.M.; Franke, S.; Stein, G.; Wolf, G. Advanced glycation end products and the kidney. Am. J. Physiol., 2005, 289(4), 645-659.
[http://dx.doi.org/10.1152/ajprenal.00398.2004 ] [PMID: 16159899 ]
[8]
Welsh, K.J.; Kirkman, M.S.; Sacks, D.B. Role of glycated proteins in the diagnosis and management of diabetes: research gaps and future directions. Diabetes Care, 2016, 39(8), 1299-1306.
[http://dx.doi.org/10.2337/dc15-2727 ] [PMID: 27457632 ]
[9]
Mir, A.R. Moinuddin, Habib, S.; Khan, F.; Alam, K.; Ali, A. Structural changes in histone H2A by methylglyoxal generate highly immunogenic amorphous aggregates with implications in auto-immune response in cancer. Glycobiology, 2015, 26(2), 129-141.
[http://dx.doi.org/10.1093/glycob/cwv082 ] [PMID: 26408820 ]
[10]
Mankarious, S.; Lee, M.; Fischer, S.; Pyun, K.H.; Ochs, H.D.; Oxelius, V.A.; Wedgwood, R.J. The half-lives of IgG subclasses and specific antibodies in patients with primary immunodeficiency who are receiving intravenously administered immunoglobulin. J. Lab. Clin. Med., 1988, 112(5), 634-640.
[PMID: 3183495]
[11]
Ercan, A.; Cui, J.; Chatterton, D.E.; Deane, K.D.; Hazen, M.M.; Brintnell, W.; O’donnell, C.I.; Derber, L.A.; Weinblatt, M.E.; Shadick, N.A.; Bell, D.A. Aberrant IgG galactosylation precedes disease onset, correlates with disease activity, and is prevalent in autoantibodies in rheumatoid arthritis. Arthritis & Rheumatism, 2010, 62(8), 2239-2248.
[http://dx.doi.org/10.1002/art.27533] [PMID: 20506563]
[12]
Austin, G.E.; Mullins, R.H.; Morin, L.G. Non-enzymic glycation of individual plasma proteins in normoglycemic and hyperglycemic patients. Clin. Chem., 1987, 33(12), 2220-2224.
[http://dx.doi.org/10.1093/clinchem/33.12.2220] [PMID: 3690840]
[13]
Dunn, E.J.; Ariëns, R.A. Fibrinogen and fibrin clot structure in diabetes. Herz, 2004, 29(5), 470-479.
[http://dx.doi.org/10.1007/s00059-004-2607-z] [PMID: 15340732]
[14]
Arfat, M.Y.; Ashraf, J.M.; Arif, Z.; Alam, K. Fine characterization of glucosylated human IgG by biochemical and biophysical methods. IJBM, 2014, 69, 408-415.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.05.069] [PMID: 24953604]
[15]
Akhter, F.; Khan, M.S.; Shahab, U.; Ahmad, S. Bio-physical characterization of ribose induced glycation: a mechanistic study on DNA perturbations. IJBM, 2013, 58, 206-210.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.03.036] [PMID: 23524157]
[16]
Ghisaidoobe, A.; Chung, S. Intrinsic tryptophan fluorescence in the detection and analysis of proteins: a focus on Förster resonance en-ergy transfer techniques. Int. J. Mol. Sci., 2014, 15(12), 22518-22538.
[http://dx.doi.org/10.3390/ijms151222518] [PMID: 25490136]
[17]
Ahmad, S.; Khan, R.H.; Ali, A. Physicochemical studies on glycation‐induced structural changes in human IgG. IUBMB Life, 2012, 64(2), 151-156.
[http://dx.doi.org/10.1002/iub.582] [PMID: 22241644]
[18]
Ashraf, J.M.; Ahmad, S.; Rabbani, G.; Hasan, Q.; Jan, A.T.; Lee, E.J.; Khan, R.H.; Alam, K.; Choi, I. 3-Deoxyglucosone: a potential glycating agent accountable for structural alteration in H3 histone protein through generation of different AGEs. PLoS One, 2015, 10(2)e0116804
[http://dx.doi.org/10.1371/journal.pone.0116804 ] [PMID: 25689368 ]
[19]
Khan, M.A.; Arif, Z.; Khan, M.A.; Alam, K. Methylglyoxal produces more changes in biochemical and biophysical properties of human IgG under high glucose compared to normal glucose level. PloS one, 2018, 13(1)e0191014
[http://dx.doi.org/10.1371/journal.pone.0191014 ] [PMID: 29351321]
[20]
Yagi, K. Lipid peroxides and human diseases. Chem. Phys. Lipids, 1987, 45, 337-351.
[http://dx.doi.org/10.1016/0009-3084(87)90071-5] [PMID: 3319232]
[21]
Khan, M.Y.; Alouffi, S.; Ahmad, S. Immunochemical studies on native and glycated LDL- An approach to uncover the structural purtabations. IJBM, 2018, 115, 287-299.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.04.016] [PMID: 29634967]
[22]
Siddiqui, Z.; Ishtikhar, M.; Ahmad, S. d-Ribose induced glycoxidative insult to hemoglobin protein: An approach to spot its structural perturbations. IJBM, 2018, 112, 134-147.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.01.161] [PMID: 29378270]
[23]
Khan, H.; Khan, M.S.; Ahmad, S. The in vivo and in vitro approaches for establishing a link between advanced glycation end products and lung cancer. J. Cell. Biochem., 2018, 119(11), 9099-9109.
[http://dx.doi.org/10.1002/jcb.27170]] [PMID: 30076739]
[24]
Ajmal, M.R.; Nusrat, S.; Alam, P.; Zaidi, N.; Badr, G.; Mahmoud, M.H.; Rajpoot, R.K.; Khan, R.H. Differential mode of interaction of ThioflavinT with native β structural motif in human α 1-acid glycoprotein and cross beta sheet of its amyloid: Biophysical and molecular docking approach. J. Mol. Struct., 2016, 1117, 208-217.
[http://dx.doi.org/10.1016/j.molstruc.2016.03.081]
[25]
Teale, F.W.J.; Weber, G. Ultraviolet fluorescence of the aromatic amino acids. Biochem. J., 1957, 65(3), 476-482.
[http://dx.doi.org/10.1042/bj0650476] [PMID: 13412650]
[26]
Peng, H.L.; Callender, R. The mechanism for fluorescence quenching of tryptophan by oxamate and pyruvate: Conjugation and solvation induced photoinduced electron transfer. J. Phys. Chem. B, 2018, 122(25), 6483-6490.
[http://dx.doi.org/10.1021/acs.jpcb.8b02433 ] [PMID: 29860828]
[27]
Shahab, U.; Ahmad, S.; Dixit, K.; Habib, S.; Alam, K.; Ali, A. Genotoxic effect of N-hydroxy-4-acetylaminobiphenyl on human DNA: implications in bladder cancer. PLoS One, 2013, 8(1)e53205
[http://dx.doi.org/10.1371/journal.pone.0053205] [PMID: 23382838]
[28]
Kong, J.; Yu, S. Fourier transform infrared spectroscopic analysis of protein secondary structures.Acta Biochim. Biophys. Sin.,, 2007, 39(8), 549-559.
[http://dx.doi.org/10.1111/j.1745-7270.2007.00320.x]
[29]
Garidel, P.; Schott, H. Fourier-transform midinfrared spectroscopy for analysis and screening of liquid protein formulations. BPI, 2006, 4(6), 48-55.
[30]
Hunt, J.V.; Bottoms, M.A.; Mitchinson, M.J. Oxidative alterations in the experimental glycation model of diabetes mellitus are due to protein-glucose adduct oxidation. Some fundamental differences in proposed mechanisms of glucose oxidation and oxidant production. Biochem. J., 1993, 291(2), 529-535.
[http://dx.doi.org/10.1042/bj2910529] [PMID: 8484733]
[31]
Ahmad, R.; Tripathi, A.K.; Tripathi, P.; Singh, S.; Singh, R.; Singh, R.K. Malondialdehyde and protein carbonyl as biomarkers for oxidative stress and disease progression in patients with chronic myeloid leukemia. in vivo, 2008, 22(4), 525-528.
[PMID: 18712183]
[32]
Triantaphyllopoulos, E.; Triantaphyllopoulos, D.C. Amino acid composition of human fibrinogen and anticoagulant derivatives. Biochem. J., 1967, 105, 393-400.
[http://dx.doi.org/10.1042/bj1050393]


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Article Details

VOLUME: 21
ISSUE: 9
Year: 2020
Published on: 11 December, 2020
Page: [916 - 923]
Pages: 8
DOI: 10.2174/1389203720666190618095719
Price: $65

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