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Acceleration of protein glycation by oxidative stress and comparative role of antioxidant and protein glycation inhibitor

  • Laxman N. Bavkar
  • Rahul S. Patil
  • Sheetalnath B. Rooge
  • Megha L. Nalawade
  • Akalpita U. ArvindekarEmail author
Article
  • 17 Downloads

Abstract

Hyperglycemia in diabetes causes protein glycation that leads to oxidative stress, release of cytokines, and establishment of secondary complications such as neuropathy, retinopathy, and nephropathy. Several other metabolic disorders, stress, and inflammation generate free radicals and oxidative stress. It is essential to study whether oxidative stress independently enhances protein glycation leading to rapid establishment of secondary complications. Oxidative stress was experimentally induced using rotenone and Fenton reagent for in vivo and in vitro studies, respectively. Results showed significant increase in the rate of modification of BSA in the form of fructosamine and protein-bound carbonyls in the presence of fenton reagent. Circular dichroism studies revealed gross structural changes in the reduction of alpha helix structure and decreased protein surface charge was confirmed by zeta potential studies. Use of rotenone demonstrated enhanced AGE formation, ROS generation, and liver and kidney tissue glycation through fluorescence measurement. Similar findings were also observed in cell culture studies. Use of aminoguanidine, a protein glycation inhibitor, demonstrated reduction in these changes; however, a combination of aminoguanidine along with vitamin E demonstrated better amelioration. Thus, oxidative stress accelerates the process of protein glycation causing gross structural changes and tissue glycation in insulin-independent tissues. Use of antioxidants and protein glycation inhibitors in combination are more effective in preventing such changes and could be an effective therapeutic option for preventing establishment of secondary complications of diabetes.

Keywords

Protein glycation Oxidative stress Fenton reaction Rotenone Aminoguanidine Vitamin E 

Abbreviations

BSA

Bovine serum albumin

Fent

Fenton reagent

Rot

Rotenone

AMG

Aminoguanidine

Vit E

Vitamin E

DCF-DA

2′,7′-Dichlorofluorescin diacetate

HuH-7

Hepatocellular carcinoma cells

SOD

Superoxide dismutase

CAT

Catalase

PCO

Protein-bound carbonyls

AGEs

Advanced Glycation End-Products

TCA

Tricarboxylic acid

CD

Circular dichroism

Notes

Acknowledgements

Laxman Naghnath Bavkar acknowledges the University Grant Commission (UGC), New Delhi, India for a fellowship under the Special Assistance Program for Basic Scientific Research. Rahul Shivaji Patil acknowledges the Department of Science and Technology (DST), New Delhi, India for DST-INSPIRE fellowship. Chemicals and research work were supported by RUSA, Government of Maharashtra funded to Prof. (Mrs.) A. U. Arvindekar. The authors are thankful to the Department of Biochemistry, Shivaji University, Kolhapur for providing work place and laboratory.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Turk Z, Ljubic S, Turk N, Benko B (2001) Detection of autoantibodies against advanced glycation end products and AGE-immune complexes in serum of patients with diabetes mellitus. Clin Chim Acta 303:105–115.  https://doi.org/10.1016/S0009-8981(00)00389-2 CrossRefGoogle Scholar
  2. 2.
    Takeuchi M, Kikuchi S, Sasaki N et al (2004) Involvement of advanced glycation end-products (AGEs) in Alzheimer’s disease. Curr Alzheimer Res 1:39–46.  https://doi.org/10.2174/1567205043480582 CrossRefGoogle Scholar
  3. 3.
    Vistoli G, De Maddis D, Cipak A et al (2013) Advanced glycoxidation and lipoxidation end products (AGES and ALES): an overview of their mechanisms of formation. Free Radic Res 47:3–27.  https://doi.org/10.3109/10715762.2013.815348 CrossRefGoogle Scholar
  4. 4.
    Brownlee M (1994) Glycation products and the pathogenesis of diabetic complications. Diabetes 43:836–841.  https://doi.org/10.2337/diab.43.6.836 CrossRefGoogle Scholar
  5. 5.
    Watkins NG, Thorpe SR, Baynes JW (1985) Glycation of amino groups in protein. Studies on the specificity of modification of RNase by glucose. J Biol Chem 260:10629–10636Google Scholar
  6. 6.
    Vitek MP, Bhattacharya K, Glendening JM et al (1994) Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Natl Acad Sci USA 91:4766–4770.  https://doi.org/10.1073/pnas.91.11.4766 CrossRefGoogle Scholar
  7. 7.
    Schmidt MA, Stern DM (2000) RAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes. Trends Endocrinol Metab 11:368–375.  https://doi.org/10.1016/S1043-2760(00)00311-8 CrossRefGoogle Scholar
  8. 8.
    Thornalley PJ, Langborg A, Minhas HS (1999) Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J 344:109–116.  https://doi.org/10.1042/bj3440109 CrossRefGoogle Scholar
  9. 9.
    Rahbar S, Figarola JL (2003) Novel inhibitors of advanced glycation end products. Arch Biochem Biophys 419:63–79.  https://doi.org/10.1016/j.abb.2003.08.009 CrossRefGoogle Scholar
  10. 10.
    Brownlee M, Vlassara H, Kooney A et al (1986) Aminoguanidine prevents diabetes-induced arterial wall protein cross-linking. Science 232:1629–1632.  https://doi.org/10.1126/science.3487117 CrossRefGoogle Scholar
  11. 11.
    Maritim AC, Sanders RA, Watkins JB (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17:24–38.  https://doi.org/10.1002/jbt.10058 CrossRefGoogle Scholar
  12. 12.
    Rival T, Page RM, Chandraratna DS, Sendall TJ, Ryder E, Liu B et al (2009) Fenton chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a Drosophila model of Alzheimer’s disease. Eur J Neurosci 29:1335–1347.  https://doi.org/10.1111/j.1460-9568.2009.06701.x CrossRefGoogle Scholar
  13. 13.
    Omar ME, Abdel-Salam Yasser AK et al (2014) Effect of a single intrastriatal rotenone injection on oxidative stress and neurodegeneration in the rat brain. Comp Clin Pathol 23:1457–1467.  https://doi.org/10.1007/s00580-013-1807-4 CrossRefGoogle Scholar
  14. 14.
    Li D, Devaraj S, Fuller C, Bucala R, Jialal I (1996) Effect of tocopherol on LDL oxidation and glycation: in vitro and in vivo studies. J Lipid Res 37:1978–1986Google Scholar
  15. 15.
    Jagdale AD, Bavkar LN et al (2016) Strong inhibition of the polyol pathway diverts glucose flux to protein glycation leading to rapid establishment of secondary complications in diabetes mellitus. J Diabetes Complicat 30:398–405CrossRefGoogle Scholar
  16. 16.
    Johnson RN, Metcalf PA, Baker JR (1983) Fructosamine: a new approach to the estimation of serum glycosylprotein: an index of diabetic control. Clin Chim Acta 127:87–95.  https://doi.org/10.1016/0009-8981(83)90078-5 CrossRefGoogle Scholar
  17. 17.
    Ansari NA, Ali R (2011) Physicochemical analysis of poly-l-lysine: an insight into the changes induced in lysine residues of proteins on modification with glucose. IUBMB Life 63:26–29.  https://doi.org/10.1002/iub.410 CrossRefGoogle Scholar
  18. 18.
    Nakamura A, Goto S (1996) Analysis of protein carbonyls with 2, 4-dinitrophenyl hydrazine and its antibodies by immunoblot in two-dimensional gel electrophoresis. J Biochem 119:768–774.  https://doi.org/10.1093/oxfordjournals.jbchem.a021306 CrossRefGoogle Scholar
  19. 19.
    Kelly SM, Price NC (2000) The use of circular dichroism in the investigation of protein structure and function. Curr Protein Pept Sci 1:349–384.  https://doi.org/10.2174/1389203003381315 CrossRefGoogle Scholar
  20. 20.
    Joglekar M, Bavkar L, Sistla S, Arvindekar A (2017) Effective inhibition of protein glycation by combinatorial usage of limonene and aminoguanidine through differential and synergistic mechanisms. Int J Biol Macromol 99:563–569.  https://doi.org/10.1016/j.ijbiomac.2017.02.104 CrossRefGoogle Scholar
  21. 21.
    Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175Google Scholar
  22. 22.
    Beers RF, Sizer IW (1952) Spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 195:133–140Google Scholar
  23. 23.
    Yeligar SM, Harris FL, Hart CM, Brown LAS (2012) Ethanol induces oxidative stress in alveolar macrophages via upregulation of NADPH oxidases. J Immunol 188:3648–3657.  https://doi.org/10.4049/jimmunol.1101278 CrossRefGoogle Scholar
  24. 24.
    Nakagawa T, Yokozawa T, Terasawa K, Shu S, Juneja LR (2002) Protective activity of green tea against free radical and glucose-mediated protein damage. J Agric Food Chem 50:2418–2422.  https://doi.org/10.1021/jf011339n CrossRefGoogle Scholar
  25. 25.
    Saengkhae C, Loetchutinat C, Garnier-Suillerot A (2003) Kinetic analysis of fluorescein and dihydrofluorescein effluxes in tumour cells expressing the multidrug resistance protein. MRP1. Biochem Pharmacol 65:969–977.  https://doi.org/10.1016/S0006-2952(02)01662-3 CrossRefGoogle Scholar
  26. 26.
    Edelstein D, Brownlee M (1992) Mechanistic studies of advanced glycation end product inhibition by aminoguanidine. Diabetes 41:26–29.  https://doi.org/10.2337/diab.41.1.26 CrossRefGoogle Scholar
  27. 27.
    Thornalley PJ (2003) Use of aminoguanidine (pimagedine) to prevent the formation of advanced glycation end products. Arch Biochem Biophys 419:31–40.  https://doi.org/10.1016/j.abb.2003.08.013 CrossRefGoogle Scholar
  28. 28.
    Goh SY, Cooper ME (2008) The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 93:1143–1152.  https://doi.org/10.1210/jc.2007-1817 CrossRefGoogle Scholar
  29. 29.
    Meerwaldt R, Links T, Zeebregts C, Tio T, Hillebrands J, Smit A (2008) The clinical relevance of assessing advanced glycation end products accumulation in diabetes. Cardiovasc Diabetol 7:29.  https://doi.org/10.1186/1475-2840-7-29 CrossRefGoogle Scholar
  30. 30.
    Vlassara H, Uribarri J (2014) Advanced glycation end products (AGE) and diabetes: cause, effect, or both? Curr Diab Rep 14:453.  https://doi.org/10.1007/s11892-013-0453-1 CrossRefGoogle Scholar
  31. 31.
    Awasthi S, Saraswathi NT (2016) Non-enzymatic glycation mediated structure-function changes in proteins: case of serum albumin. Rsc Adv 6:90739–90753.  https://doi.org/10.1039/C6RA08283A CrossRefGoogle Scholar
  32. 32.
    Greifenhagen U, Frolov A, Blüher M, Hoffmann R (2016) Site-specific analysis of advanced glycation end products in plasma proteins of type 2 diabetes mellitus patients. Anal Bioanal Chem 408:5557–5566.  https://doi.org/10.1007/s00216-016-9651-4 CrossRefGoogle Scholar
  33. 33.
    Miyata T, Kurokawa K, De Strihou CVY (2000) Advanced glycation and lipoxidation end products: role of reactive carbonyl compounds generated during carbohydrate and lipid metabolism. J Am Soc Nephrol 11:1744–1752Google Scholar
  34. 34.
    Hunt JV, Wolff SP (1991) Oxidative glycation and free radical production: a causal mechanism of diabetic complications. Free Radic Res Commun 1:115–123.  https://doi.org/10.3109/10715769109145775 CrossRefGoogle Scholar
  35. 35.
    Aronson D, Rayfield EJ (2008) How hyperglycemia promotes atherosclerosis: molecular mechanisms. Cardiovasc Diabetol 2:89.  https://doi.org/10.1186/1475-2840-1-1 Google Scholar
  36. 36.
    Verdile G, Keane KN, Cruzat VF et al (2015) Inflammation and oxidative stress: the molecular connectivity between insulin resistance, obesity, and Alzheimer’s disease. Mediat Inflamm 2:89.  https://doi.org/10.1155/2015/105828 Google Scholar
  37. 37.
    Namioka N, Hanyu H, Hirose D et al (2017) Oxidative stress and inflammation are associated with physical frailty in patients with Alzheimer’s disease. Geriatr Geriatr Gerontol Int 17:913–918.  https://doi.org/10.1111/ggi.12804 CrossRefGoogle Scholar
  38. 38.
    Plucińska K, Dekeryte R, Koss D et al (2016) Neuronal human BACE1 knockin induces systemic diabetes in mice. Diabetologia 59:1513–1523.  https://doi.org/10.1007/s00125-016-3960-1 CrossRefGoogle Scholar
  39. 39.
    Kanti Das T, Wati MR, Fatima-Shad K (2015) Oxidative stress gated by Fenton and Haber Weiss reactions and its association with Alzheimer’s disease. Arch Neurosci 2:e20078.  https://doi.org/10.1007/s00125-016-3960-1 Google Scholar
  40. 40.
    Patil RS, Jagdale AD, Nalawade ML et al (2018) Glycation inhibitors and probiotics can ameliorate the changes caused by high fructose feed. Int J Pharm Pharm Sci 10:28–32.  https://doi.org/10.22159/ijpps.2018v10i7.26870 CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Laxman N. Bavkar
    • 1
  • Rahul S. Patil
    • 1
  • Sheetalnath B. Rooge
    • 1
  • Megha L. Nalawade
    • 1
  • Akalpita U. Arvindekar
    • 1
    Email author
  1. 1.Department of BiochemistryShivaji UniversityKolhapurIndia

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