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Effect of glycation on alpha-crystallin structure and chaperone-like function
P Anil Kumar1, M Satish Kumar, G Bhanuprakash Reddy
1Biochemistry Division, National Institute of Nutrition, Hyderabad 500 007, India.
The Biochemical Journal
|August 19, 2007
Summary
Non-enzymatic glycation of alpha-crystallin by sugars like glucose and fructose impairs its chaperone function, contributing to cataract formation in aging and diabetes. This study details how different glycating agents affect alpha-crystallin structure and activity.
Area of Science:
- Biochemistry
- Ophthalmology
- Molecular Biology
Background:
- Alpha-crystallin's chaperone-like activity is crucial for maintaining eye lens transparency.
- Impaired chaperone function of alpha-crystallin, due to aging and diabetes, leads to cataract formation.
- Post-translational modifications, particularly non-enzymatic glycation, affect alpha-crystallin's chaperone function.
Purpose of the Study:
- To investigate the in vitro effects of major glycating agents (glucose, fructose, G6P, MGO) on alpha-crystallin structure and chaperone function.
- To understand how different sugars and their derivatives impact alpha-crystallin's susceptibility to glycation and subsequent functional loss.
Main Methods:
- In vitro modification of alpha-crystallin with glucose, fructose, glucose 6-phosphate (G6P), and methylglyoxal (MGO).
- Analysis of protein structure, advanced glycation end-products (AGEs) formation (including N(epsilon)-(carboxymethyl)lysine - CML), protein cross-linking, and high-molecular-mass (HMM) aggregation.
- Assays to evaluate chaperone activity using protein aggregation and enzyme inactivation methods.
Main Results:
- Glycation with all four agents formed glycated protein, increased AGE fluorescence, induced cross-linking, and HMM aggregation.
- Fructose and MGO caused significant conformational changes, while glucose and G6P showed minimal structural perturbation.
- Glycation generally decreased chaperone activity, with notable loss in enzyme inactivation assays, associated with reduced hydrophobicity.
Conclusions:
- Alpha-crystallin is susceptible to non-enzymatic glycation by various sugars and derivatives, implicated in cataractogenesis.
- The extent of structural and functional impairment varies depending on the specific glycating agent.
- Glycation-induced changes in alpha-crystallin contribute to the loss of lens transparency observed in diabetes and aging.
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