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Non-enzymatic glycation of α-crystallin as an in vitro model for aging, diabetes and degenerative diseases

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Abstract

Alpha crystallin, a small heat-shock protein, has been studied extensively for its chaperone function. Alpha crystallin subunits are expressed in stress conditions and have been found to prevent apoptosis by inhibiting the activation of caspase pathway. Non-enzymatic glycation of protein leads to the formation of advanced glycation end-products (AGEs). These AGEs bind to receptors and lead to blocking the signaling pathways or cause protein precipitation as observed in aggregation-related diseases. Methylglyoxal (MGO) is one of the major glycating agents expressed in pathological conditions due to defective glycolysis pathway. MGO reacts rapidly with proteins, forms AGEs and finally leads to aggregation. The goal of this study was to understand the non-enzymatic glycation-induced structural damage in alpha crystallin using biophysical and spectroscopic characterization. This will help to develop better disease models for understanding the biochemical pathways and also in drug discovery.

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Acknowledgments

The authors acknowledge the support from The Advanced Photon Source at Argonne supported by the US Department of Energy Office of Science under contract DE-AC02-06CH11357. We also thank Alec Sandy and Suresh Narayanan for assistance with the synchrotron X-ray data. The authors thank Hao Guo for his technical support.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, USA

    Devi Kalyan Karumanchi & Elizabeth R. Gaillard

  2. Department of Physics, Northern Illinois University, DeKalb, USA

    Nuwan Karunaratne, Laurence Lurio & James P. Dillon

  3. Department of Biological Sciences, Northern Illinois University, 1425 W Lincoln Hwy, DeKalb, IL, 60115, USA

    Elizabeth R. Gaillard

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  1. Devi Kalyan Karumanchi
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  2. Nuwan Karunaratne
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Correspondence to Elizabeth R. Gaillard.

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J. P. Dillon: In memoriam.

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Karumanchi, D.K., Karunaratne, N., Lurio, L. et al. Non-enzymatic glycation of α-crystallin as an in vitro model for aging, diabetes and degenerative diseases. Amino Acids 47, 2601–2608 (2015). https://doi.org/10.1007/s00726-015-2052-8

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