Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Influence of Ascorbic Acid on the Structure and Function of Alpha-2- macroglobulin: Investigations using Spectroscopic and Thermodynamic Techniques

Author(s): Syed Saqib Ali, Mohammad Khalid Zia, Tooba Siddiqui, Haseeb Ahsan and Fahim Halim Khan*

Volume 27, Issue 3, 2020

Page: [201 - 209] Pages: 9

DOI: 10.2174/0929866526666191002113525

Price: $65

Abstract

Background: Ascorbic acid is a classic dietary antioxidant which plays an important role in the body of human beings. It is commonly found in various foods as well as taken as dietary supplement.

Objective: The plasma ascorbic acid concentration may range from low, as in chronic or acute oxidative stress to high if delivered intravenously during cancer treatment. Sheep alpha-2- macroglobulin (α2M), a human α2M homologue is a large tetrameric glycoprotein of 630 kDa with antiproteinase activity, found in sheep’s blood.

Methods: In the present study, the interaction of ascorbic acid with alpha-2-macroglobulin was explored in the presence of visible light by utilizing various spectroscopic techniques and isothermal titration calorimetry (ITC).

Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between ascorbic acid and α2M apparent by increased absorbance and decreased fluorescence. Secondary structural changes in the α2M were investigated by CD and FT-IR spectroscopy. Our findings suggest the induction of subtle conformational changes in α2M induced by ascorbic acid. Thermodynamics signatures of ascorbic acid and α2M interaction indicate that the binding is an enthalpy-driven process.

Conclusion: It is possible that ascorbic acid binds and compromises antiproteinase activity of α2M by inducing changes in the secondary structure of the protein.

Keywords: alpha-2-macroglobulin, ascorbic acid, fourier transform infrared spectroscopy, circular dichroism, isothermal titration calorimetry.

« Previous Next »
Graphical Abstract

[1]
Noctor, G.; Foyer, C.H. Ascorbate and glutathione: Keeping active oxygen under control. Annu. Rev. Plant Physiol. Plant Mol. Biol., 1998, 49, 249-279.
[http://dx.doi.org/10.1146/annurev.arplant.49.1.249] [PMID: 15012235]
[2]
Buettner, G.R. The pecking order of free radicals and antioxidants: Lipid peroxidation, α-tocopherol, and ascorbate. Arch. Biochem. Biophys., 1993, 300(2), 535-543.
[http://dx.doi.org/10.1006/abbi.1993.1074] [PMID: 8434935]
[3]
Halliwell, B.; Gutteridge, J.M. The definition and measurement of antioxidants in biological systems. Free Radic. Biol. Med., 1995, 18(1), 125-126.
[http://dx.doi.org/10.1016/0891-5849(95)91457-3] [PMID: 7896166]
[4]
Poljšak, B.; Gazdag, Z.; Jenko-Brinovec, S.; Fujs, S.; Pesti, M.; Bélagyi, J.; Plesničar, S.; Raspor, P. Pro-oxidative vs antioxidative properties of ascorbic acid in chromium(VI)-induced damage: An in vivo and in vitro approach. J. Appl. Toxicol., 2005, 25(6), 535-548.
[http://dx.doi.org/10.1002/jat.1093] [PMID: 16092082]
[5]
Retsky, K.L.; Frei, B. Vitamin C prevents metal ion-dependent initiation and propagation of lipid peroxidation in human low-density lipoprotein. Biochim. Biophys. Acta, 1995, 1257(3), 279-287.
[http://dx.doi.org/10.1016/0005-2760(95)00089-U] [PMID: 7647104]
[6]
Padayatty, S.J.; Levine, M. New insights into the physiology and pharmacology of vitamin C. CMAJ, 2001, 164(3), 353-355.
[PMID: 11232136]
[7]
Neves, D.; Estrozi, L.F.; Job, V.; Gabel, F.; Schoehn, G.; Dessen, A. Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3. PLoS One, 2012, 7(4)e35384
[http://dx.doi.org/10.1371/journal.pone.0035384] [PMID: 22530012]
[8]
Rehman, A.A.; Ahsan, H.; Khan, F.H. α-2-Macroglobulin: A physiological guardian. J. Cell. Physiol., 2013, 228(8), 1665-1675.
[http://dx.doi.org/10.1002/jcp.24266] [PMID: 23086799]
[9]
Lin, Z.; Lo, A.; Simeone, D.M.; Ruffin, M.T.; Lubman, D.M. An N-glycosylation analysis of human alpha-2-macroglobulin using an integrated approach. J. Proteomics Bioinform., 2012, 5, 127-134.
[http://dx.doi.org/10.4172/jpb.1000224] [PMID: 23028207]
[10]
Mehl, J.W.; O’Connell, W.; Degroot, J. Macroglobulin from human plasma which forms an enzymaticaliy active compound with trypsin. Science, 1964, 145(3634), 821-822.
[http://dx.doi.org/10.1126/science.145.3634.821] [PMID: 14163324]
[11]
Rehman, A.A.; Ahsan, H.; Khan, F.H. Identification of a new alpha-2-macroglobulin: Multi-spectroscopic and isothermal titration calorimetry study. Int. J. Biol. Macromol., 2016, 83, 366-375.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.11.043] [PMID: 26608004]
[12]
Witmer, J.R.; Wetherell, B.J.; Wagner, B.A.; Du, J.; Cullen, J.J.; Buettner, G.R. Direct spectrophotometric measurement of supra-physiological levels of ascorbate in plasma. Redox Biol., 2016, 8, 298-304.
[http://dx.doi.org/10.1016/j.redox.2016.02.004] [PMID: 26928133]
[13]
Shamsi, A.; Shahwan, M.; Husain, F.M.; Khan, M.S. Characterization of methylglyoxal induced advanced glycation end products and aggregates of human transferrin: Biophysical and microscopic insight. Int. J. Biol. Macromol., 2019, 138, 718-724.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.07.140] [PMID: 31351151]
[14]
Ali, S.S.; Zia, M.K.; Siddiqui, T.; Ahsan, H.; Khan, F.H. Biophysical analysis of interaction between curcumin and alpha-2-macroglobulin. Int. J. Biol. Macromol., 2019, 128, 385-390.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.01.136] [PMID: 30690117]
[15]
Shamsi, A.; Al Shahwan, M.; Ahamad, S.; Hassan, M.I.; Ahmad, F.; Islam, A. Spectroscopic, calorimetric and molecular docking insight into the interaction of Alzheimer’s drug donepezil with human transferrin: Implications of Alzheimer’s drug. J. Biomol. Struct. Dyn., 2019, 1-9.
[http://dx.doi.org/10.1080/07391102.2019.1595728] [PMID: 30898045]
[16]
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]
[17]
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]
[18]
Ali, S.S.; Zia, M.K.; Siddiqui, T.; Khan, F.H. Binding interaction of sheep alpha-2-macroglobulin and tannic acid: A spectroscopic and thermodynamic study. Spectrochim. Acta Part A: Mol. Biomol. Spectrosc., 2018, 204(5), 748-753.
[http://dx.doi.org/10.1016/j.saa.2018.06.024]
[19]
Xu, H.; Liu, Q.; Zuo, Y.; Bi, Y.; Gao, S. Spectroscopic studies on the interaction of Vitamin C with bovine serum albumin. J. Solution Chem., 2009, 38, 15-25.
[20]
Zaidi, N.; Ajmal, M.R.; Rabbani, G.; Ahmad, E.; Khan, R.H. A Comprehensive insight into binding of Hippuric acid to human serum albumin: A study to uncover its impaired elimination through hemodialysis. PLoS One, 2013, 8(8)e71422
[http://dx.doi.org/10.1371/journal.pone.0071422] [PMID: 23951159]
[21]
Kelly, S.M.; Price, N.C. The use of circular dichroism in the investigation of protein structure and function. Curr. Protein Pept. Sci., 2000, 1(4), 349-384.
[http://dx.doi.org/10.2174/1389203003381315] [PMID: 12369905]
[22]
Fleming, D.J.; Tucker, K.L.; Jacques, P.F.; Dallal, G.E.; Wilson, P.W.; Wood, R.J. Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort. Am. J. Clin. Nutr., 2002, 76(6), 1375-1384.
[http://dx.doi.org/10.1093/ajcn/76.6.1375] [PMID: 12450906]
[23]
Frei, B.; England, L.; Ames, B.N. Ascorbate is an outstanding antioxidant in human blood plasma. Proc. Natl. Acad. Sci. USA, 1989, 86(16), 6377-6381.
[http://dx.doi.org/10.1073/pnas.86.16.6377] [PMID: 2762330]
[24]
Halliwell, B. Antioxidants in human health and disease. Annu. Rev. Nutr., 1996, 16, 33-50.
[http://dx.doi.org/10.1146/annurev.nu.16.070196.000341] [PMID: 8839918]
[25]
Na, N.; Delanghe, J.R.; Taes, Y.E.; Torck, M.; Baeyens, W.R.; Ouyang, J. Serum vitamin C concentration is influenced by haptoglobin polymorphism and iron status in Chinese. Clin. Chim. Acta, 2006, 365(1-2), 319-324.
[http://dx.doi.org/10.1016/j.cca.2005.09.015] [PMID: 16256097]
[26]
Padayatty, S.J.; Levine, M.; Vitamin, C.; Vitamin, C. The known and the unknown and Goldilocks. Oral Dis., 2016, 22(6), 463-493.
[http://dx.doi.org/10.1111/odi.12446] [PMID: 26808119]
[27]
Buresova, V.; Hajdusek, O.; Franta, Z.; Sojka, D.; Kopacek, P. IrAM-An α2-macroglobulin from the hard tick Ixodes ricinus: Characterization and function in phagocytosis of a potential pathogen Chryseobacterium indologenes. Dev. Comp. Immunol., 2009, 33(4), 489-498.
[http://dx.doi.org/10.1016/j.dci.2008.09.011] [PMID: 18948134]
[28]
Barrera, D.I.; Matheus, L.M.; Stigbrand, T.; Arbeláez, L.F. Proteolytic hydrolysis and purification of the LRP/alfa-2-macroglobulin receptor domain from α-macroglobulins. Protein Expr. Purif., 2007, 53(1), 112-118.
[http://dx.doi.org/10.1016/j.pep.2006.12.008] [PMID: 17257854]
[29]
Lu, Y.; Wang, G.; Lu, X.; Lv, J.; Xu, M.; Zhang, W. Molecular mechanism of interaction between norfloxacin and trypsin studied by molecular spectroscopy and modeling. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2010, 75(1), 261-266.
[http://dx.doi.org/10.1016/j.saa.2009.10.021] [PMID: 19910245]
[30]
Li, X.; Wang, G.; Chen, D.; Lu, Y. Binding of ascorbic acid and α-tocopherol to bovine serum albumin: A comparative study. Mol. Biosyst., 2014, 10(2), 326-337.
[http://dx.doi.org/10.1039/C3MB70373H] [PMID: 24310979]
[31]
Sulkowska, A. Interaction of drugs with bovine and human serum albumin. J. Mol. Struct., 2002, 614, 227-232.
[http://dx.doi.org/10.1016/S0022-2860(02)00256-9]
[32]
Han, X-L.; Tian, F-F.; Ge, Y-S.; Jiang, F-L.; Lai, L.; Li, D-W.; Yu, Q-L.; Wang, J.; Lin, C.; Liu, Y. Spectroscopic, structural and thermodynamic properties of chlorpyrifos bound to serum albumin: A comparative study between BSA and HSA. J. Photochem. Photobiol. B, 2012, 109, 1-11.
[http://dx.doi.org/10.1016/j.jphotobiol.2011.12.010] [PMID: 22316628]
[33]
Lakowicz, J.R. Fluorescence anisotropy.In: Principles of Fluorescence Spectroscopy; Springer: Boston, MA, 2006, pp. 291-319.
[http://dx.doi.org/10.1007/978-1-4757-3061-6_10]
[34]
Miller, J.N. Recent advances in molecular luminescence analysis. Proc. Anal. Div. Chem. Soc., 1979, 16(7), 203-208.
[35]
Samari, F.; Hemmateenejad, B.; Shamsipur, M.; Rashidi, M.; Samouei, H. Affinity of two novel five-coordinated anticancer Pt(II) complexes to human and bovine serum albumins: A spectroscopic approach. Inorg. Chem., 2012, 51(6), 3454-3464.
[http://dx.doi.org/10.1021/ic202141g] [PMID: 22364149]
[36]
Divsalar, A.; Bagheri, M.J.; Saboury, A.A.; Mansoori-Torshizi, H.; Amani, M. Investigation on the interaction of newly designed anticancer Pd(II) complexes with different aliphatic tails and human serum albumin. J. Phys. Chem. B, 2009, 113(42), 14035-14042.
[http://dx.doi.org/10.1021/jp904822n] [PMID: 19778061]
[37]
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]
[38]
Tian, J.; Liu, J.; He, W.; Hu, Z.; Yao, X.; Chen, X. Probing the binding of scutellarin to human serum albumin by circular dichroism, fluorescence spectroscopy, FTIR, and molecular modeling method. Biomacromolecules, 2004, 5(5), 1956-1961.
[http://dx.doi.org/10.1021/bm049668m] [PMID: 15360311]

Rights & Permissions Print Cite
Article Metrics
15
© 2024 Bentham Science Publishers | Privacy Policy