title: The structural alteration and aggregation propensity of glycated lens crystallins in the presence of calcium: Importance of lens calcium homeostasis in development of diabetic cataracts.
abstract: The imbalance of the calcium homeostasis in the lenticular tissues of diabetic patients is an important risk factor for development of cataract diseases. In the current study, the impact of elevated levels of calcium ions were investigated on structure and aggregation propensity of glycated lens crystallins using gel electrophoresis and spectroscopic assessments. The glycated proteins indicated significant resistance against calcium-induced structural insults and aggregation. While, glycated crystallins revealed an increased conformational stability; a slight instability was observed for these proteins upon interaction with calcium ions. Also, in the presence of calcium, the proteolytic pattern of native crystallins was altered and that of glycated protein counterparts remained almost unchanged. According to results of this study it is suggested that the structural alteration of lens crystallins upon glycation may significantly reduce their calcium buffering capacity in eye lenses. Therefore, under chronic hyperglycemia accumulation of this cataractogenic metal ion in the lenticular tissues may subsequently culminate in activation of different pathogenic pathways, leading to development of lens opacity and cataract diseases.
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Sara Zafaranchi
authors.initials: SZ
authors.lastname: Zm
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Kazem
authors.initials: K
authors.lastname: Khoshaman
authors.affiliation: Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Raheleh
authors.initials: R
authors.lastname: Masoudi
authors.affiliation: Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Bahram
authors.initials: B
authors.lastname: Hemmateenejad
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran. Electronic address: ryousefi@shirazu.ac.ir.
authors.forename: Reza
authors.initials: R
authors.lastname: Yousefi
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism*; D002386:Cataract / Q000150:complications / Q000473:pathology*; D002417:Cattle; D002918:Chymotrypsin / Q000378:metabolism; D002942:Circular Dichroism; D003432:Cross-Linking Reagents / Q000737:chemistry; D003459:Crystallins / Q000737:chemistry*; D003920:Diabetes Mellitus / Q000473:pathology*; D000067493:Dynamic Light Scattering; D005453:Fluorescence; D006031:Glycosylation; D006706:Homeostasis; D007477:Ions; D007700:Kinetics; D007908:Lens, Crystalline / Q000737:chemistry*; D008970:Molecular Weight; D066329:Protein Aggregates; D011487:Protein Conformation; D055550:Protein Stability; D059748:Proteolysis; D013844:Thiazoles / Q000737:chemistry; D014364:Tryptophan / Q000378:metabolism
chemical_list: D052160:Benzothiazoles; D003432:Cross-Linking Reagents; D003459:Crystallins; D007477:Ions; D066329:Protein Aggregates; D013844:Thiazoles; C009462:thioflavin T; D014364:Tryptophan; D002918:Chymotrypsin; D002118:Calcium
keywords: Aggregation; Calcium; Cataract; Diabetes; Lens crystallins