Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

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

Research Article

Effect of Antioxidants on Heavy Metals Induced Conformational Alteration of Cytochrome C and Myoglobin

Author(s): Khadega Khamis Moh Alazoumi, Anwar Ahmed, Salman Freeh Alamery, Anas Shamsi, Basir Ahmad, Asimul Islam* and Humaira Farooqi*

Volume 28 , Issue 1 , 2021

Published on: 10 June, 2020

Page: [31 - 42] Pages: 12

DOI: 10.2174/0929866527666200610134442

Price: $65

Abstract

Background: The exposure to heavy metals due to unrestrained industrialization, pollution and non-degradability imposes a significant risk to human health. Proteins are prime targets of heavy metal stress, however, the underlying mechanisms and its impact on heme proteins is still not entirely clear.

Objective: To analyze the deleterious effect of heavy metals such as cadmium, chromium and mercury on conformation of two proteins namely, cytochrome c and myoglobin. The protective effect of glycine and ascorbic acid (animal origin), gallic acid and sesamol (plant origin) on heavy metal exposure was studied.

Methods: Far- and near-UV Circular Dichroism (CD) measurements monitored the changes in secondary and tertiary structure. Absorption Soret spectroscopy study revealed changes in heme-protein interaction. Peroxidase activity has been assayed to measure the absorption of tetraguaiacol. The interaction of heme proteins with different heavy metals was done using docking study.

Results: Far- and near-UV CD measurements reveal that heavy metals disrupt the secondary and tertiary structure of heme proteins. Antioxidants counteract the deleterious effect of heavy metals. Absorption spectroscopy revealed changes in the Soret region of these heme proteins. Changes in peroxidase activity was observed on addition of heavy metals and antioxidants. Molecular docking validated interaction of the heavy metals with proteins with a significant binding affinity (-2.3 kcal/- mol).

Conclusion: Heavy metals interfered and disrupted both the heme proteins and mercury showed the maximum deleterious effect, further, chromium showed detrimental effect at very small concentration. The antioxidants from animal origin exhibited better protective response than those from plant source.

Keywords: Cytochrome c, myoglobin, heavy metals, protein structure, protein denaturation, antioxidants.

Graphical Abstract
[1]
Jaishankar, M.; Tseten, T.; Anbalagan, N.; Mathew, B.B.; Beeregowda, K.N. Toxicity, mechanism and health effects of some heavy metals. Interdiscip. Toxicol., 2014, 7, 60-72.
[2]
Lambert, M.; Leven, B.A.; Green, R.M. 2000. Available from: https://cfpub.epa.gov/ncer_abstracts/index.cfm/fuseaction/display.files/fileID/14295
[3]
Jacobson, T. Cadmium causes misfolding and aggregation of cytosolic proteins in yeast. Mol. Cell. Biol., 2017, 37, e00490-e16.
[http://dx.doi.org/10.1128/MCB.00490-16]
[4]
Desai, V.; Kaler, S.G. Role of copper in human neurological disorders. Am. J. Clin. Nutr., 2008, 88, 855S-858S.
[http://dx.doi.org/10.1093/ajcn/88.3.855S]
[5]
Vlasova, I.I. Peroxidase activity of human hemoproteins: Keeping the fire under control. Molecules, 2018, 23, 1-27.
[6]
Shamsi, A.; Mohammad, T.; Khan, M.S.; Shahwan, M.; Husain, F.M.; Rehman, M.T.; Hassan, M.I.; Ahmad, F.; Islam, A. Unraveling binding mechanism of Alzheimer’s drug rivastigmine tartrate with human transferrin: Molecular docking and multi-spectroscopic approach towards neurodegenerative diseases. Biomolecules, 2019, 9(9), 495.
[7]
Schatz, G. Mitochondrial oxidative phosphorylation. Angew. Chem. Int. Ed. Engl., 1967, 6, 1035-1046.
[http://dx.doi.org/10.1002/anie.196710351]
[8]
Agbas, A. Trends of protein aggregation in neurodegenerative diseases, , 2018.
[9]
Koseoglu, E.; Koseoglu, R.; Kendirci, M.; Saraymen, R.; Saraymen, B. Trace metal concentrations in hair and nails from Alzheimer’s disease patients: Relations with clinical severity. J. Trace Elem. Med. Biol., 2017, 39, 124-128.
[10]
Drahansky, M.; Paridah, M.; Moradbak, A.; Mohamed, A. We are IntechOpen, the world’ s leading publisher of Open Access books Built by scientists, for scientists TOP 1; Intech, 2016, p. 13.
[11]
Tamás, M.J.; Sharma, S.K.; Ibstedt, S.; Jacobson, T.; Christen, P. Heavy metals and metalloids as a cause for protein misfolding and aggregation. Biomolecules, 2014, 4, 252-267.
[12]
Kim, A.C.; Lim, S.; Kim, Y.K. Metal ion effects on Aβ and tau aggregation. Int. J. Mol. Sci., 2018, 19, 1-15.
[http://dx.doi.org/10.3390/ijms19010128]
[13]
Järup, L. Hazards of heavy metal contamination. Br. Med. Bull., 2003, 68, 167-182.
[http://dx.doi.org/10.1093/bmb/ldg032]
[14]
Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev., 2010, 4(8), 118.
[http://dx.doi.org/10.4103/0973-7847.70902]
[15]
Flora, S.J.S.; Mittal, M.; Mehta, A. Heavy metal induced oxidative stress & its possible reversal by chelation therapy. Indian J. Med. Res., 2008, 128(4), 501-523.
[16]
Palaniappan, R.; Muthulingam, M. Effect of heavy metal, chromium on protein and amino acid 450 contents in gill, liver and kidney of freshwater fish, Channa striatus (Bloch). Int. J. Curr. Microbiol. Appl. Sci., 2016, 5(7), 372-382.
[17]
Flora, S.J.S. Nutritional components modify metal absorption, toxic response and chelation therapy. J. Nutr. Environ. Med., 2002, 12, 53-67.
[18]
Aungst, B.J.; Fung, H.L. The effects of dietary calcium on lead absorption, distribution, and elimination kinetics in rats. J. Toxicol. Environ. Health, 1985, 16(1), 147-159.
[19]
Flora, S.J.S.; Tandon, S.K. Preventive and therapeutic effects of thiamine, ascorbic acid and their combination in lead intoxication. Acta Pharmacol. Toxicol. (Copenh.), 1986, 58(5), 374-378.
[20]
Oh, S.H.; Lim, S.C. A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. Toxicol. Appl. Pharmacol., 2006, 212(3), 212-223.
[21]
Mohajeri, M.; Rezaee, M.; Sahebkar, A. Cadmium-induced toxicity is rescued by curcumin: A review. Biofactors, 2017, 43, 645-661.
[22]
Wang, Z.; Zhang, J.; Chen, L.; Li, J.; Zhang, H.; Guo, X. Glycine suppresses AGE/RAGE signaling athway and subsequent oxidative stress by restoring Glo1 function in the aorta of diabetic rats and in HUVECs. Oxid. Med. Cell. Longev., 2019, 46, 28962.
[23]
Geetha, T.; Rohit, B.; Pal, K. Sesamol: An efficient antioxidant with potential therapeutic benefits. Med. Chem., 2009, 5, 367-371.
[24]
Micali, A. Flavocoxid, a natural antioxidant, protects mouse kidney from cadmium-induced toxicity. Oxid. Med. Cell. Longev., 2018, 2018, 9162946.
[25]
Goto, Y.; Takahashi, N.; Fink, A.L. Mechanism of acid-induced folding of proteins. Biochemistry, 1990, 29, 3480-3488.
[http://dx.doi.org/10.1021/bi00466a009]
[26]
Puett, D. The Equilibrium unfolding parameters of horse and sperm whale myoglobin. J. Biol. Chem., 1973, 248, 4263-4634.
[27]
Narra, H.P.; Cordes, M.H.J.; Ochman, H. Structural features and the persistence of acquired proteins. Proteomics, 2008, 8, 4772-4781.
[28]
Kuroda, Y.; Hamada, D.; Tanaka, T.; Goto, Y. High helicity of peptide fragments corresponding to 479 β-strand regions of β-lactoglobulin observed by 2D-NMR spectroscopy. Fold. Des., 1996, 1, 255-263.
[29]
Sharma, G.S.; Warepam, M.; Bhattacharya, R.; Singh, L.R. Covalent modification by glyoxals converts Cytochrome C into its apoptotically competent state. Sci. Rep., 2019, 9, 1-8.
[30]
Schrodinger, L.L.C. The PyMOL molecular graphics system. Version, 2010, 1(5)
[31]
Guex, N.; Peitsch, M.C. SWISS-MODEL and the Swiss-PdbViewer: An environment for comparative protein modeling. Electrophoresis, 1997, 18, 2714-2723.
[32]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256]
[33]
Rai, P.K.; Lee, S.S.; Zhang, M.; Tsang, Y.F.; Kim, K.H. Heavy metals in food crops: Health risks, fate, mechanisms, and management. Environ. Int., 2019, 125, 365-385.
[34]
Greenfield, N.J. Circular dichroism analysis for protein-protein interactions. Methods Mol. Biol., 2004, 261, 55-78.
[35]
Parray, Z.A.; Shahid, S.; Ahmad, F.; Hassan, M.I.; Islam, A. Characterization of intermediate state of myoglobin in the presence of PEG 10 under physiological conditions. Int. J. Biol. Macromol., 2017, 99, 241-248.
[36]
Khan, S.H.; Islam, A.; Hassan, M.I.; Sharma, S.; Singh, T.P.; Ahmad, F. Effect of conservative mutations (L94V and L94I) on the structure and stability of horse Cytochrome C. Arch. Biochem. Biophys., 2017, 633, 40-49.
[http://dx.doi.org/10.1016/j.abb.2017.08.015]
[37]
Kito, H.; Ose, Y.; Sato, T. Cadmium-binding protein (metallothionein) in carp. Environ. Health Perspect., 1986, 65, 117-124.
[38]
Kondoh, M.; Ogasawara, S.; Araragi, S.; Higashimoto, M.; Sato, M. Cytochrome C release from mitochondria induced by cadmium. J. Health Sci., 2001, 47(1), 78-82.
[39]
Bent, P.; Hospital, B. Metallothionein: A cadmium and zinc-containing protein from equine renal cortex. J. Biol. Chem., 1961, 236(9), 508.
[40]
Mizrahi, L.; Achituv, Y. Effect of heavy metals ions on enzyme activity in the mediterranean mussel, Donax trunculus. Bull. Environ. Contam. Toxicol., 1989, 42, 854-859.
[41]
Alnuaimi, M.M.; Saeed, I.A.; Ashraf, S.S. Effect of various heavy metals on the enzymatic activity of E. coli alkaline phosphatase. Int. J. Biotechnol. Biochem., 2012, 8(1), 973-2691.
[42]
Shamsi, A.; Ahmed, A.; Khan, M.S.; Husain, F.M.; Amani, S.; Bano, B. Investigating the interaction of anticancer drug temsirolimus with human transferrin: Molecular docking and spectroscopic 516 517 518 approach. J. Mol. Recognit., 2018, 31(10), 1-7.
[http://dx.doi.org/10.1002/jmr.2728]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy