title: Protective effects of carnosine on dehydroascorbate-induced structural alteration and opacity of lens crystallins: important implications of carnosine pleiotropic functions to combat cataractogenesis.
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.
authors.affiliation: a Protein Chemistry Laboratory (PCL), Department of Biology , College of Sciences, Shiraz University , Shiraz , Iran.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Javadi
authors.affiliation: a Protein Chemistry Laboratory (PCL), Department of Biology , College of Sciences, Shiraz University , Shiraz , Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Yousefi
authors.affiliation: b Faculty of Biological Sciences, Department of Biochemistry , Tarbiat Modares University , Tehran , Iran.
authors.forename: Saman
authors.initials: S
authors.lastname: Hosseinkhani
authors.affiliation: c Center for Nanotechnology in Drug Delivery, School of Pharmacy , Shiraz University of Medical Sciences , Shiraz , Iran.
authors.forename: Ali-Mohammad
authors.initials: AM
authors.lastname: Tamaddon
authors.affiliation: d Department of Molecular Medicine and Byrd Alzheimer's Research Institute, Morsani College of Medicine , University of South Florida , Tampa , FL 33612 , USA.
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002336:Carnosine / Q000494:pharmacology*; D002386:Cataract / Q000378:metabolism / Q000517:prevention & control; D002417:Cattle; D003683:Dehydroascorbic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D024202:Electrophoretic Mobility Shift Assay; D006031:Glycosylation / Q000187:drug effects; D007908:Lens, Crystalline / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D046509:Tissue Culture Techniques; D038201:alpha-Crystallins / Q000737:chemistry*; D038222:gamma-Crystallins / Q000737:chemistry*
chemical_list: D020011:Protective Agents; D038201:alpha-Crystallins; D038222:gamma-Crystallins; D002336:Carnosine; D001241:Aspirin; D003683:Dehydroascorbic Acid
keywords: aggregation; carnosine; dehydroascorbic acid (DHA); senile cataracts; α-crystallin