Protective Effects of Carnosine on Dehydroascorbate-induced Structural Alteration and Opacity of Lens Crystallins: Important Implications of Carnosine Pleiotropic Functions to Combat Cataractogenesis
Document Type
Article
Publication Date
2017
Keywords
dehydroascorbic acid (DHA), α-crystallin, carnosine, aggregation, senile cataracts
Digital Object Identifier (DOI)
https://doi.org/10.1080/07391102.2016.1194230
Abstract
The high level of dehydroascorbic acid (DHA) in the lenticular tissue is an important risk factor for the development of age-related cataracts. In this study, the effects of DHA on structure and function of lens crystallins were studied in the presence of carnosine using gel mobility shift assay, different spectroscopic techniques, and lens culture analysis. The DHA-induced unfolding and aggregation of lens proteins were largely prevented by this endogenous dipeptide. The ability of carnosine to preserve native protein structure upon exposure to DHA suggests the essential role of this dipeptide in prevention of the senile cataract development. Although the DHA-modified α-crystallin was characterized by altered chaperone activity, functionality of this protein was significantly restored in the presence of carnosine. The increased proteolytic instability of DHA-modified lens proteins was also attenuated in the presence of carnosine. Furthermore, the assessment of lens culture suggested that DHA can induce significant lens opacity which can be prevented by carnosine. These observations can be explained by the pleiotropic functions of this endogenous and pharmaceutical compound, notably by its anti-glycation and anti-aggregation properties. In summary, our study suggests that carnosine may have therapeutic potential in preventing senile cataracts linked with the increased lenticular DHA generation, particularly under pathological conditions associated with the oxidative stress.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
Journal of Biomolecular Structure and Dynamics, v. 35, issue 8, p. 1766-1784
Scholar Commons Citation
Javadi, Sajjad; Yousefi, Reza; Hosseinkhani, Saman; Tamaddon, Ali-Mohammad; and Uversky, Vladimir N., "Protective Effects of Carnosine on Dehydroascorbate-induced Structural Alteration and Opacity of Lens Crystallins: Important Implications of Carnosine Pleiotropic Functions to Combat Cataractogenesis" (2017). Molecular Medicine Faculty Publications. 325.
https://digitalcommons.usf.edu/mme_facpub/325
