Relationship between the Structure and Chaperone Activity of Human αA-Crystallin after Its Modification with Diabetes-Associated Oxidative Agents and Protective Role of Antioxidant Compounds

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Sogand Sasan Moghadam¹, Maryam Ghahramani¹, Kazem Khoshaman¹, Ahmad Oryan², Ali Akbar Moosavi-Movahedi³, Boris I. Kurganov^4#, and Reza Yousefi^1,3,a*

¹Protein Chemistry Laboratory, Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran

²Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran

³Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran

⁴Bach Institute of Biochemistry, Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russia

^* To whom correspondence should be addressed.

^# Deceased.

Received September 12, 2021; Revised October 16, 2021; Accepted October 16, 2021

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The study was aimed to evaluate the impact of peroxynitrite (PON, oxidative stress agent in diabetes), methylglyoxal (MGO, diabetes-associated reactive carbonyl compound), and their simultaneous application on the structural and functional features of human αA-crystallin (αA-Cry) using various spectroscopy techniques. Additionally, the surface tension and oligomer size distribution of the treated and untreated protein were tested using tensiometric analysis and dynamic light scattering, respectively. Our results indicated that the reaction of PON and MGO with human αA-Cry leads to the formation of new chromophores, alterations in the secondary to quaternary protein structure, reduction in the size of protein oligomers, and significant enhancement in the chaperone activity of αA-Cry. To reverse the effects of the tested compounds, ascorbic acid and glutathione (main components of lens antioxidant defense system) were applied. As expected, the two antioxidant compounds significantly prevented formation of high molecular weight aggregates of αA-Cry (according to SDS-PAGE). Our results suggest that the lens antioxidant defense system, in particular, glutathione, may provide a strong protection against rapid incidence and progression of diabetic cataract by preventing the destructive reactions of highly reactive DM-associated metabolites.

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Keywords: human αA-crystallin, diabetic cataract, lens antioxidant, protein structure, chaperone activity

DOI: 10.1134/S000629792202002X

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