The THE ROLE OF ASTAXANTHIN COMPARED WITH METFORMIN IN PREVENTING GLYCATED HUMAN SERUM ALBUMIN FROM POSSIBLE UNFOLDING: A MOLECULAR DYNAMIC STUDY
DOI:
https://doi.org/10.22159/ajpcr.2019.v12i9.34617Keywords:
Astaxanthin, Glycated human serum albumin, Metformin, Molecular Dynamic,, Root mean square deviation, Root mean square fluctuationAbstract
Objectives: Albumin in diabetes mellitus undergoes conformational changes that affect the ability as an endogenous scavenger. Treatment with astaxanthin (ASX) expected to improve the function of albumin in case of diabetes mellitus. The objectives of this study are to compare the capability of ASX and metformin to prevent conformational changes on glycated albumin.
Methods: Data mining is performed to obtain human serum albumin (HSA) (4K2C), glucose (79025), ASX (5281224), and metformin (4091). Data preparation used PyRx and Discovery Studio 2016 Client. PyRx is utilized for docking and analysis of receptor-ligand interactions with LigPlus and Discovery Studio 2016 Client. YASARA is used for molecular dynamics simulations with a running time of 15.000 ps.
Results: A description of the glycated-HSA (gHSA) conformational changes that are bound to metformin has been successfully carried out. Changes that occur were unfolding and release of bonds in gHSA. Unfolding on gHSA includes the release of bonds between sites A and B. The root mean square deviation (RMSD) backbone value of metformin-gHSA shows a significant difference with gHSA at 8650 ps where gHSA showed 6.47 nm while the metformin-gHSA was 8.06 nm and continues to increase up to 15.72 nm at the end of the simulation. RMSD and root mean square fluctuation residues of gHSA which were interacted with ASX showed conditions close to normal HSA. In 11725 ps ASX-gHSA remained stable at 5.78 nm, whereas gHSA increased to 8.13 nm. gHSA at the end of the simulation showed a number of 9.052 nm while the normal HSA was 7.561 nm.
Conclusion: This result indicated that ASX prevents gHSA from possible unfolding.
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References
Bullon P, Newman HN, Battino M. Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: A shared pathology via oxidative stress and mitochondrial dysfunction? Periodontol 2000 2014;64:139-53.
Murray RK, Granner DK, Mayes PA, Rodwell VW. Harper’s Illustrated Biochemistry. 26th ed. Boston: McGraw Hills Companies; 2003. p. 609-12.
Roche M, Rondeau P, Singh NR, Tarnus E, Bourdon E. The antioxidant properties of serum albumin. FEBS Lett 2008;582:1783-7.
Dobson CM. The structural basis of protein folding and its links with human disease. Philos Trans R Soc Lond B Biol Sci 2001;356:133-45.
Otagiri M, Chuang VT. Albumin in Medicine: Pathological and Clinical Applications. Singapore: Springer Nature; 2016.
Merlot AM, Kalinowski DS, Richardson DR. Unraveling the mysteries of serum albumin-more than just a serum protein. Front Physiol 2014;5:299.
Barnaby OS, Cerny RL, Clarke W, Hage DS. Comparison of modification sites formed on human serum albumin at various stages of glycation. Clin Chim Acta 2011;412:277-85.
Arasteh A, Farahi S, Habibi-Rezaei M, Moosavi-Movahedi AA. Glycated albumin: An overview of the in vitro models of an in vivo potential disease marker. J Diabetes Metab Disord 2014;13:49.
Hirst JA, Farmer AJ, Ali R, Roberts NW, Stevens RJ. Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care 2012;35:446-54.
Holman R. Metformin as first choice in oral diabetes treatment: The UKPDS experience. Journ Annu Diabetol Hotel Dieu 2007;13:13-20.
Grisouard J, Timper K, Radimerski TM, Frey DM, Peterli R, Kola B, et al. Mechanisms of metformin action on glucose transport and metabolism in human adipocytes. Biochem Pharmacol 2010;80:1736-45.
Woo SL, Xu H, Li H, Zhao Y, Hu X, Zhao J, et al. Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity. PLoS One 2014;9:e91111.
Wang YW, He SJ, Feng X, Cheng J, Luo YT, Tian L, et al. Metformin: A review of its potential indications. Drug Des Devel Ther 2017;11:2421-9.
Nishigaki I, Rajendran P, Venugopal R, Ekambaram G, Sakthisekaran D, Nishigaki Y, et al. Cytoprotective role of astaxanthin against glycated protein/iron chelate-induced toxicity in human umbilical vein endothelial cells. Phytother Res 2010;24:54-9.
Sudhamalla B, Gokara M, Ahalawat N, Amooru DG, Subramanyam R. Molecular dynamics simulation and binding studies of beta-sitosterol with human serum albumin and its biological relevance. J Phys Chem B 2010;114:9054-62.
Artali R, Bombieri G, Calabi L, Del Pra A. A molecular dynamics study of human serum albumin binding sites. Farmaco 2005;60:485-95.
Rahnama E, Mahmoodian-Moghaddam M, Khorsand-Ahmadi S, Saberi MR, Chamani J. Binding site identification of metformin to human serum albumin and glycated human serum albumin by spectroscopic and molecular modeling techniques: A comparison study. J Biomol Struct Dyn 2015;33:513-33.
Jayanti GE, Widyarti S, Sabarudin A, Sumitro SB. Egg white albumin form complex with aspirin and caffeine and its role as free radical scavenger. Asian J Pharm Clin Res 2018;11:340-4.
Krieger E, Vriend G. YASARA view - molecular graphics for all devices - from smartphones to workstations. Bioinformatics 2014;30:2981-2.
Yue Y, Chen X, Qin J, Yao X. Characterization of the mangiferin-human serum albumin complex by spectroscopic and molecular modeling approaches. J Pharm Biomed Anal 2009;49:753-9.
Verma R, Jatav VK, Sharma S. Identification of inhibitors of dengue virus (DENV1, DENV2 and DENV3) NS2B/NS3 serine protease: A molecular docking and simulation approach. Asian J Pharm Clin Res 2015;8:287-92.
Fujiwara S, Amisaki T. Identification of high affinity fatty acid binding sites on human serum albumin by MM-PBSA method. Biophys J 2008;94:95-103.
Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in Type 2 diabetes mellitus. Cochrane Database Syst Rev 2010;4:CD002967.
Vecchio S, Protti A. Metformin-induced lactic acidosis: No one left behind. Crit Care 2011;15:107.
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