Glyoxal Induced Transition of Transferrin to Aggregates: Spectroscopic, Microscopic and Molecular Docking Insight

Author(s): Anas Shamsi, Khan M. Abdullah, Hina Usmani, Areeba Shahab, Hamza Hasan, Imrana Naseem*

Journal Name: Current Pharmaceutical Biotechnology

Volume 20 , Issue 12 , 2019

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Abstract:

Background & Objective: The present study was aimed at characterizing the conformational alterations induced in human transferrin, the iron regulatory protein by glyoxal. Since protein aggregation is at the core of many disorders, thus interest in this domain has increased significantly during the past years.

Methods: In our present study, the effect of glyoxal was monitored on human transferrin using multispectroscopic and multi-microscopic studies.

Results: Intrinsic fluorescence spectroscopy suggested changes in native conformation of human transferrin evident by decreased fluorescence and blue shift in the presence of glyoxal. Further, extrinsic fluorescence was retorted and the results showed the formation of aggregates; apparent by increased Congo red (CR) absorbance, Thioflavin T (ThT) and ANS fluorescence and TEM of human transferrin in the presence of glyoxal. Molecular docking was also employed to see which residues are at core of human transferrin and glyoxal interaction. Reactive oxygen species (ROS) generation assays revealed enhanced ROS levels by human transferrin after treatment with glyoxal.

Conclusion: Thus, our study proposes that glyoxal induces the formation of aggregates in human transferrin. These aggregates further generate ROS which are key players in the complications associated with diabetes mellitus, giving our study clinical perspective.

Keywords: Human transferrin, spectroscopy, microscopy, molecular docking, reactive oxygen species, glyoxal.

[1]
Onuchic, J.N.; Wolynes, P.G. Theory of protein folding. Curr. Opin. Struct. Biol., 2004, 14(1), 70-75.
[http://dx.doi.org/10.1016/j.sbi.2004.01.009] [PMID: 15102452]
[2]
Aisen, P.; Leibman, A.; Zweier, J. Stoichiometric and site characteristics of the binding of iron to human transferrin. J. Biol. Chem., 1978, 253(6), 1930-1937.
[PMID: 204636]
[3]
Chung, M.C.M. Structure and function of transferrin. Biochem. Educ., 1984, 12, 146-154.
[http://dx.doi.org/10.1016/0307-4412(84)90118-3]
[4]
CHARLOTEAUX‐WAUTERS M. Iron transport and storage. Eur. J. Biochem., 1987, 164, 485-506.
[http://dx.doi.org/10.1111/j.1432-1033.1987.tb11155.x]
[5]
Sipe, J.D. Amyloidosis. Annu. Rev. Biochem., 1992, 61, 947-975.
[http://dx.doi.org/10.1146/annurev.bi.61.070192.004503] [PMID: 1497327]
[6]
Carrell, R.W.; Lomas, D.A. Conformational disease. Lancet, 1997, 350(9071), 134-138.
[http://dx.doi.org/10.1016/S0140-6736(97)02073-4] [PMID: 9228977]
[7]
De Young, L.R.; Dill, K.A.; Fink, A.L. Aggregation and denaturation of apomyoglobin in aqueous urea solutions. Biochemistry, 1993, 32(15), 3877-3886.
[http://dx.doi.org/10.1021/bi00066a006] [PMID: 8471600]
[8]
Tennent, G.A.; Lovat, L.B.; Pepys, M.B. Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. Proc. Natl. Acad. Sci. USA, 1995, 92(10), 4299-4303.
[http://dx.doi.org/10.1073/pnas.92.10.4299] [PMID: 7753801]
[9]
Iram, A.; Naeem, A. Trifluoroethanol and acetonitrile induced formation of the molten globule states and aggregates of cellulase. Int. J. Biol. Macromol., 2012, 50(4), 932-938.
[http://dx.doi.org/10.1016/j.ijbiomac.2012.02.012] [PMID: 22679632]
[10]
Shahab, U.; Tabrez, S.; Khan, M.S.; Akhter, F.; Khan, M.S.; Saeed, M.; Ahmad, K.; Srivastava, A.K.; Ahmad, S. Immunogenicity of DNA-advanced glycation end product fashioned through glyoxal and arginine in the presence of Fe3: Its potential role in prompt recognition of diabetes mellitus auto-antibodies. Chem. Biol. Interact., 2014, 219, 229-240.
[http://dx.doi.org/10.1016/j.cbi.2014.06.012] [PMID: 24968179]
[11]
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]
[12]
Pool-Zobel, B.L.; Guigas, C.; Klein, R.; Neudecker, C.; Renner, H.W.; Schmezer, P. Assessment of genotoxic effects by lindane. Food Chem. Toxicol., 1993, 31(4), 271-283.
[http://dx.doi.org/10.1016/0278-6915(93)90077-C] [PMID: 7682977]
[13]
Ahmed, A.; Shamsi, A.; Bano, B. Characterizing harmful advanced glycation end-products (AGEs) and ribosylated aggregates of yellow mustard seed phytocystatin: Effects of different monosaccharides. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2017, 171, 183-192.
[http://dx.doi.org/10.1016/j.saa.2016.08.004] [PMID: 27526342]
[14]
Hawe, A.; Sutter, M.; Jiskoot, W. Extrinsic fluorescent dyes as tools for protein characterization. Pharm. Res., 2008, 25(7), 1487-1499.
[http://dx.doi.org/10.1007/s11095-007-9516-9] [PMID: 18172579]
[15]
Chi, Z.; Liu, R. Phenotypic characterization of the binding of tetracycline to human serum albumin. Biomacromolecules, 2011, 12(1), 203-209.
[http://dx.doi.org/10.1021/bm1011568] [PMID: 21142141]
[16]
Guan, J.; Yan, X.; Zhao, Y.; Sun, Y.; Peng, X. Binding studies of triclocarban with bovine serum albumin: Insights from multi-spectroscopy and molecular modeling methods. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2018, 202, 1-12.
[http://dx.doi.org/10.1016/j.saa.2018.04.070] [PMID: 29777928]
[17]
Peng, X.; Wang, X.; Qi, W.; Su, R.; He, Z. Affinity of rosmarinic acid to human serum albumin and its effect on protein conformation stability. Food Chem., 2016, 192, 178-187.
[http://dx.doi.org/10.1016/j.foodchem.2015.06.109] [PMID: 26304336]
[18]
Eisert, R.; Felau, L.; Brown, L.R. Methods for enhancing the accuracy and reproducibility of Congo red and thioflavin T assays. Anal. Biochem., 2006, 353(1), 144-146.
[http://dx.doi.org/10.1016/j.ab.2006.03.015] [PMID: 16620754]
[19]
Iram, A.; Amani, S.; Furkan, M.; Naeem, A. Equilibrium studies of cellulase aggregates in presence of ascorbic and boric acid. Int. J. Biol. Macromol., 2013, 52, 286-295.
[http://dx.doi.org/10.1016/j.ijbiomac.2012.10.023] [PMID: 23107806]
[20]
Abdullah, K.M.; Qais, F.A.; Ahmad, I.; Hasan, H.; Naseem, I. Study of pyridoxamine against glycation and reactive oxygen species production in human serum albumin as model protein: An in vitro & ex vivo approach. Int. J. Biol. Macromol., 2018, 120(Pt B), 1734-1743.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.09.176] [PMID: 30268752]
[21]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[22]
Pandya, P.; Agarwal, L.K.; Gupta, N.; Pal, S. Molecular recognition pattern of cytotoxic alkaloid vinblastine with multiple targets. J. Mol. Graph. Model., 2014, 54, 1-9.
[http://dx.doi.org/10.1016/j.jmgm.2014.09.001] [PMID: 25241127]
[23]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19, 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B]
[24]
Stsiapura, V.I.; Maskevich, A.A.; Kuzmitsky, V.A.; Uversky, V.N.; Kuznetsova, I.M.; Turoverov, K.K. Thioflavin T as a molecular rotor: fluorescent properties of thioflavin T in solvents with different viscosity. J. Phys. Chem. B, 2008, 112(49), 15893-15902.
[http://dx.doi.org/10.1021/jp805822c] [PMID: 19367903]
[25]
Khurana, R.; Coleman, C.; Ionescu-Zanetti, C.; Carter, S.A.; Krishna, V.; Grover, R.K.; Roy, R.; Singh, S. Mechanism of thioflavin T binding to amyloid fibrils. J. Struct. Biol., 2005, 151(3), 229-238.
[http://dx.doi.org/10.1016/j.jsb.2005.06.006] [PMID: 16125973]
[26]
Wu, C.; Wang, Z.; Lei, H.; Zhang, W.; Duan, Y. Dual binding modes of Congo red to amyloid protofibril surface observed in molecular dynamics simulations. J. Am. Chem. Soc., 2007, 129(5), 1225-1232.
[http://dx.doi.org/10.1021/ja0662772] [PMID: 17263405]
[27]
Amani, S.; Shamsi, A.; Rabbani, G.; Naim, A. An insight into the biophysical characterization of insoluble collagen aggregates: Implication for arthritis. J. Fluoresc., 2014, 24(5), 1423-1431.
[http://dx.doi.org/10.1007/s10895-014-1424-x] [PMID: 25011697]
[28]
Bannister, W.; Bannister, J. Circular dichroism and protein structure. Int. J. Biochem., 1974, 5, 673-677.
[http://dx.doi.org/10.1016/0020-711X(74)90052-4]
[29]
Greenfield, N.; Fasman, G.D. Computed circular dichroism spectra for the evaluation of protein conformation. Biochemistry, 1969, 8(10), 4108-4116.
[http://dx.doi.org/10.1021/bi00838a031] [PMID: 5346390]
[30]
Sreerama, N.; Woody, R.W. Estimation of protein secondary structure from circular dichroism spectra: Comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set. Anal. Biochem., 2000, 287(2), 252-260.
[http://dx.doi.org/10.1006/abio.2000.4880] [PMID: 11112271]
[31]
Saxena, V.P.; Wetlaufer, D.B. A new basis for interpreting the circular dichroic spectra of proteins. Proc. Natl. Acad. Sci. USA, 1971, 68(5), 969-972.
[http://dx.doi.org/10.1073/pnas.68.5.969] [PMID: 5280530]
[32]
Yang, Y.; Zhang, X.; Wang, X.; Zhao, X.; Ren, T.; Wang, F.; Yu, B. Enhanced delivery of artemisinin and its analogues to cancer cells by their adducts with human serum transferrin. Int. J. Pharm., 2014, 467(1-2), 113-122.
[http://dx.doi.org/10.1016/j.ijpharm.2014.03.044] [PMID: 24661944]


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VOLUME: 20
ISSUE: 12
Year: 2019
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DOI: 10.2174/1389201020666190731122806
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