Abstract
Loss of eye lens transparency due to cataract is the leading cause of blindness all over the world. While aggregation of lens crystallins is the most common endpoint in various types of cataracts, chaperone-like activity (CLA) of α-crystallin preventing protein aggregation is considered to be important for maintaining the eye lens transparency. Osmotic stress due to increased accumulation of sorbitol under hyperglycemic conditions is believed to be one of the mechanisms for diabetic cataract. In addition, compromised CLA of α-crystallin in diabetic cataract has been reported. However, the effect of sorbitol on the structure and function of α-crystallin has not been elucidated yet. Hence, in the present exploratory study, we described the effect of varying concentrations of sorbitol on the structure and function of α-crystallin. Alpha-crystallin purified from the rat lens was incubated with varying concentrations of sorbitol in the dark under sterile conditions for up to 5 days. At the end of incubation, structural properties and CLA were evaluated by spectroscopic methods. Interestingly, different concentrations of sorbitol showed contrasting results: at lower concentrations (5 and 50 mM) there was a decrease in CLA and subtle alterations in secondary and tertiary structure but not at higher concentrations (500 mM). Though, these results shed a light on the effect of sorbitol on α-crystallin structure–function, further studies are required to understand the mechanism of the observed effects and their implication to cataractogenesis.
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Abbreviations
- AR:
-
aldose reductase
- CD:
-
circular dichroism
- CLA:
-
chaperone-like activity
- DSC:
-
differential scanning calorimetry
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Acknowledgments
GBR is supported by grants from the Indian Council of Medical Research, the Department of Biotechnology and the Science & Engineering Research Board, Government of India. Research done at the University of Hyderabad was supported by University Grants Commission (India) through UPE-II and CAS programs, and the Department of Science and Technology (India) through the PURSE and FIST programs. CUK and US are supported by a research fellowship from the Indian Council of Medical Research and VS is supported by a research fellowship from the Council for Scientific & Industrial Research, Government of India.
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Kumar, C.U., Suryavanshi, U., Sontake, V. et al. Effect of Sorbitol on Alpha-Crystallin Structure and Function. Biochemistry Moscow 87, 131–140 (2022). https://doi.org/10.1134/S0006297922020055
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DOI: https://doi.org/10.1134/S0006297922020055