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Effect of glycation on human serum albumin–zinc interaction: a biophysical study

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Abstract

Zinc deficiency is common in diabetes. However, the cause of this phenomenon is largely unknown. 80% of the absorbed zinc is transported through the blood in association with human serum albumin (HSA). Under persistent hyperglycemia, HSA frequently undergoes non-enzymatic glycation which can affect its structure and metal-binding function. Hence, in this study, we have examined the interaction of zinc with native and glycated HSA. The protein samples were incubated either in the presence or in the absence of physiologically elevated glucose concentration for 21 days. The samples were then analyzed for structural changes and zinc-binding ability using various spectrometric and calorimetric approaches. The study reveals changes in the three-dimensional structure of the protein upon glycation that cause local unfolding of the molecule. Most such regions are localized in subdomain IIA of HSA which plays a key role in zinc binding. This affects zinc interaction with HSA and could in part explain the perturbed zinc distribution in patients with hyperglycemia. The varying degree of HSA glycation in blood could explain the observed heterogeneity pertaining to zinc deficiency among people suffering from diabetes.

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References

  1. King J, Cousins RJ (2005) Zinc. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ (eds) Modern nutrition in health and disease, 10th edn. Lippincott Williams and Wilkins, Baltimore, pp 271–285

    Google Scholar 

  2. Prasad AS (1985) Clinical manifestations of zinc deficiency. Annu Rev Nutr 5:341–363

    Article  CAS  PubMed  Google Scholar 

  3. Roohani N, Hurrell R, Kelishadi R, Schulin R (2013) Zinc and its importance for human health: an integrative review. J Res Med Sci. 18:144–157

    PubMed  PubMed Central  Google Scholar 

  4. Kelleher SL, McCormick NH, Velasquez V, Lopez V (2011) Zinc in specialized secretory tissues: roles in the pancreas, prostate, and mammary gland. Adv Nutr. 2:101–111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Prasad AS (1991) Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Nutr 53:403–412

    Article  CAS  PubMed  Google Scholar 

  6. Islam MR, Arslan I, Attia J, McEvoy M, McElduff P, Basher A, Rahman W, Peel R, Akhter A, Akter S, Vashum KP, Milton AH (2013) Is serum zinc level associated with prediabetes and diabetes?: a cross-sectional study from Bangladesh. PLoS One 17(8):e61776

    Article  Google Scholar 

  7. Kinlaw WB, Levine AS, Morley JE, Silvis SE, McClain CJ (1983) Abnormal zinc metabolism in type II diabetes mellitus. Am J Med 75:273–277

    Article  CAS  PubMed  Google Scholar 

  8. Kechrid Z, Demir N, Abdennour C, Bouzerna N (2002) Effect of low dietary zinc intake and experimental diabetes on the zinc and carbohydrate metabolism in rats. Turks J Med Sci. 32:101–105

    CAS  Google Scholar 

  9. Sun Q, van Dam RM, Willett WC, Hu FB (2009) Prospective study of zinc intake and risk of type 2 diabetes in women. Diabetes Care 32:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Himoto T, Yoneyama H, Deguch A, Kurokohchi K, Inuka M, Masugata H, Goda F, Senda S, Watanabe S, Kubota S, Kuriyama S, Masaki T (2010) Insulin resistance derived from zinc deficiency in non-diabetic patients with chronic hepatitis C. Exp Ther Med 1:707–711

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Myers SA, Nield A, Myers M (2012) Zinc transporters, mechanisms of action and therapeutic utility: implications for type 2 diabetes mellitus. J Nutr Metab 2012:173712

    Article  PubMed  PubMed Central  Google Scholar 

  12. Jayawardena R, Ranasinghe P, Galappatthy P, Malkanthi RLDK, Constantine GR, Katulanda P (2012) Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr. 4:13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Niewoehner CB, Allen JI, Boosalis M, Levine AS, Morley JE (1986) Role of zinc supplementation in type II diabetes mellitus. Am J Med 81:63–68

    Article  CAS  PubMed  Google Scholar 

  14. Afkhami-Ardekani M, Karimi M, Mohammadi SM, Nourani F (2008) Effect of zinc sulfate supplementation on lipid and glucose in type 2 diabetic patients. Pak J Nutr. 7:550–553

    Article  CAS  Google Scholar 

  15. Al-Maroof RA, Al-Sharbatti SS (2006) Serum zinc levels in diabetic patients and effect of zinc supplementation on glycemic control of type 2 diabetics. Saudi Med J 27:344–350

    PubMed  Google Scholar 

  16. Ioannidis JP (2005) Contradicted and initially stronger effects in highly cited clinical research. JAMA 294:218–228

    Article  CAS  PubMed  Google Scholar 

  17. Wong CP, Magnusson KR, Ho E (2013) Increased inflammatory response in aged mice is associated with age-related zinc deficiency and zinc transporter dysregulation. J Nutr Biochem 24:353–359

    Article  CAS  PubMed  Google Scholar 

  18. Rondeau P, Bourdon E (2011) The glycation of albumin: structural and functional impacts. Biochimie 93:645–658

    Article  CAS  PubMed  Google Scholar 

  19. Iqbal S, Naseem I (2016) Pancreatic cancer control: is vitamin D the answer. Eur J Cancer Prev 25:188–195

    CAS  PubMed  Google Scholar 

  20. Vlassara H (2005) Advanced glycation in health and disease: role of the modern environment. Ann N Y Acad Sci 1043:452–460

    Article  CAS  PubMed  Google Scholar 

  21. Ulrich P, Cerami A (2001) Protein glycation, diabetes, and aging. Recent Prog Horm Res 56:1–22

    Article  CAS  PubMed  Google Scholar 

  22. King JC, Shames DM, Lowe NM, Woodhouse LR, Sutherland B, Abrams SA, Turnlund JR, Jackson MJ (2001) Effect of acute zinc depletion on zinc homeostasis and plasma zinc kinetics in men. Am J Clin Nutr 74:116–124

    Article  CAS  PubMed  Google Scholar 

  23. Iqbal S, Alam MM, Naseem I (2016) Vitamin D prevents glycation of proteins: an in vitro study. FEBS Lett 590:2725–2736

    Article  CAS  PubMed  Google Scholar 

  24. Levine H (1999) Quantification of beta-sheet amyloid fibril structures with thioflavin T. Methods Enzymol 309:274–284

    Article  CAS  PubMed  Google Scholar 

  25. Sedlak J, Lindsay RH (1968) Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205

    Article  CAS  PubMed  Google Scholar 

  26. Guo M, Li H, Zhang Y, Shao S, Guo M, Wang X (2015) Study on the interaction of zinc ion binding with human serum albumin using isothermal titration calorimetry. J Chem Soc Pak 37:452–457

    CAS  Google Scholar 

  27. Bera R, Sahoo BK, Ghosh KS, Dasgupta S (2008) Studies on the interaction of isoxazolcurcumin with calf thymus DNA. Int J Biol Macromol 42(1):14–21

    Article  CAS  PubMed  Google Scholar 

  28. Ahmad I, Ahmad A, Ahmad M (2016) Binding properties of pendimethalin herbicide to DNA: multispectroscopic and molecular docking approaches. Phys Chem Chem Phys 18(9):6476–6485

    Article  CAS  PubMed  Google Scholar 

  29. Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, Olson AJ (1998) Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem 19:1639–1662

    Article  CAS  Google Scholar 

  30. Ling X, Zhong W, Huang Q, Ni K (2008) Spectroscopic studies on the interaction of pazufloxacin with calf thymus DNA. J Photochem Photobiol B 93:172–176

    Article  CAS  PubMed  Google Scholar 

  31. Kalaivani P, Prabhakaran R, Kaveri MV, Huang R, Staples RJ, Natarajan K (2013) Synthesis, spectral, X-ray crystallography, electrochemistry, DNA/Protein binding and radical scavenging activity of new palladium(II) complexes containing triphenylarsine. Inorg Chim Acta 405:415–426

    Article  CAS  Google Scholar 

  32. Iqbal S, Khan S, Naseem I (2017) Antioxidant role of vitamin D in mice with alloxan-induced diabetes. Can J Diab. (in press)

  33. Kechrid Z, Hamdi M, Nazıroğlu M, Flores-Arce M (2012) Vitamin D supplementation modulates blood and tissue zinc, liver glutathione and blood biochemical parameters in diabetic rats on a zinc-deficient diet. Biol Trace Elem Res 148:371–377

    Article  CAS  PubMed  Google Scholar 

  34. Ohyoshi E, Hamada Y, Nakata K, Kohata S (1999) The interaction between human and bovine serum albumin and zinc studied by a competitive spectrophotometry. J Inorg Biochem 75:213–218

    Article  CAS  PubMed  Google Scholar 

  35. Butkus JM, O’Riley S, Chohan BS, Basu S (2016) Interaction of small zinc complexes with globular proteins and free tryptophan. Inter J Spectrosc 2016:1–12

    Article  Google Scholar 

  36. Bolattin MB, Nandibewoor ST, Joshi SD, Dixit SR, Chimatadar SA (2016) Interaction of hydralazine with human serum albumin and effect of β-cyclodextrin on binding: insights from spectroscopic and molecular docking techniques. Ind Eng Chem Res 55:5454–5464

    Article  CAS  Google Scholar 

  37. Gaudreau S, Neault JF, Tajmir-Riahi HA (2002) Interaction of AZT with human serum albumin studied by capillary electrophoresis, FTIR and CD spectroscopic methods. J Biomol Struct Dyn 19:2007–2014

    Article  Google Scholar 

  38. Cheng Z, Liu R, Jiang X (2013) Spectroscopic studies on the interaction between tetrandrine and two serum albumins by chemometrics methods. Spectrochim Acta A Mol Biomol Spectrosc. 115:92–105

    Article  CAS  PubMed  Google Scholar 

  39. Chen M, Liu Y, Cao H, Song L, Zhang Q (2015) the secondary and aggregation structural changes of BSA induced by trivalent chromium: a biophysical study. J Lumin 158:116–124

    Article  CAS  Google Scholar 

  40. Joshi VOD, Joshi NV, Gil H, Velasquez W, Contreras S, Màrquez G (1999) Assessment of nonenzymatic glycation in proteins by FTIR spectroscopy. Proceedings of the SPIE, vol 3608. pp 240–246

  41. Wang Q, Huang CR, Jiang M, Zhu YY, Wang J, Chen J, Shi JH (2016) Binding interaction of atorvastatin with bovine serum albumin: spectroscopic methods and molecular docking. Spectrochim Acta Part A Mol Biomol Spectrosc 156:155–163

    Article  CAS  Google Scholar 

  42. Stewart AJ, Blindauer CA, Berezenko S, Sleep D, Sadler PJ (2003) Interdomain zinc site on human albumin. PNAS 100:3701–3706

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ebert JC, Altman RB (2008) Robust recognition of zinc binding sites in proteins. Protein Sci 17(1):54–65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Handing KB, Shabalin IG, Kassaar O, Khazaipoul S, Blindauer CA, Stewart AJ, Chruszcz M, Minor W (2016) Circulatory zinc transport is controlled by distinct interdomain sites on mammalian albumins. Chem. Sci. 7:6635–6648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Sudlow GD, Birkett DJ, Wade DN (1975) The characterization of two specific drug binding sites on human serum albumin. Mol Pharmacol 11:824–832

    CAS  PubMed  Google Scholar 

  46. Trzaskowski B, Adamowicz L, Deymier PA (2008) A theoretical study of zinc (II) interactions with amino acid models and peptide fragments. J Biol Inorg Chem 13:133–137

    Article  CAS  PubMed  Google Scholar 

  47. Blindauer CA, Harvey I, Bunyan KE, Stewart AJ, Sleep D, Harrison DJ, Berezenko S, Sadler PJ (2009) Structure, properties, and engineering of the major zinc binding site on human albumin. J Biol Chem 284:23116–23124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Arasteh A, Farahi S, Habibi-Rezaei M, Moosavi-Movahedi AA (2014) Glycated albumin: an overview of the in vitro models of an in vivo potential disease marker. J Diabetes Metab Disord. 13:49

    Article  PubMed  PubMed Central  Google Scholar 

  49. Barnaby OS, Cerny RL, Clarke W, Hage DS (2011) Comparison of modification sites formed on human serum albumin at various stages of glycation. Clin Chim Acta 412:277–285

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are thankful to Shumaila Khan for helping with protein studies and in editing the manuscript. Sarah Iqbal is funded through UGC-SRF Scheme, Govt. of India and acknowledges the grant support.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India

    Sarah Iqbal, Md. Maroof Alam & Imrana Naseem

  2. Department of Agricultural Microbiology, Aligarh Muslim University, Aligarh, UP, 202002, India

    Faizan Abul Qais

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  1. Sarah Iqbal
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  2. Faizan Abul Qais
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  3. Md. Maroof Alam
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  4. Imrana Naseem
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Contributions

SI and IN designed the study. SI designed the protocols. Experiments were carried out by SI, FAQ, and MA. SI and FAQ analyzed the data and wrote the manuscript with inputs from IN.

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Correspondence to Imrana Naseem.

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Iqbal, S., Qais, F.A., Alam, M.M. et al. Effect of glycation on human serum albumin–zinc interaction: a biophysical study. J Biol Inorg Chem 23, 447–458 (2018). https://doi.org/10.1007/s00775-018-1554-8

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