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J Biomol Struct Dyn. 2017 Jun;35(8):1766-1784. doi: 10.1080/07391102.2016.1194230. Epub 2016 Aug 19.

Protective effects of carnosine on dehydroascorbate-induced structural alteration and opacity of lens crystallins: important implications of carnosine pleiotropic functions to combat cataractogenesis.

Author information

1
a Protein Chemistry Laboratory (PCL), Department of Biology , College of Sciences, Shiraz University , Shiraz , Iran.
2
b Faculty of Biological Sciences, Department of Biochemistry , Tarbiat Modares University , Tehran , Iran.
3
c Center for Nanotechnology in Drug Delivery, School of Pharmacy , Shiraz University of Medical Sciences , Shiraz , Iran.
4
d Department of Molecular Medicine and Byrd Alzheimer's Research Institute, Morsani College of Medicine , University of South Florida , Tampa , FL 33612 , USA.

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.

KEYWORDS:

aggregation; carnosine; dehydroascorbic acid (DHA); senile cataracts; α-crystallin

PMID:
27472261
DOI:
10.1080/07391102.2016.1194230
[Indexed for MEDLINE]

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