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.
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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
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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.
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Bavkar, L.N., Patil, R.S., Rooge, S.B. et al. Acceleration of protein glycation by oxidative stress and comparative role of antioxidant and protein glycation inhibitor. Mol Cell Biochem 459, 61–71 (2019). https://doi.org/10.1007/s11010-019-03550-7
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DOI: https://doi.org/10.1007/s11010-019-03550-7