title: Assessment of structure, stability and aggregation of soluble lens proteins and alpha-crystallin upon non-enzymatic glycation: The pathomechanisms underlying cataract development in diabetic patients.
abstract: Total soluble lens proteins (TSPs) and α-crystallin (α-Cry) were individually subjected to the long-term glycation in the presence of d-glucose. The glycated and non-glycated protein counterparts were incubated under different stress conditions and compared according to their structure, stability and aggregation propensity by various spectroscopic techniques and gel mobility shift analyses. Extensive glycation of the lens proteins was accompanied with structural alteration, reduction in their surface hydrophobicity and increment of their surface tension. Our results suggest that glycation causes lens crystallins to partially resist against structural alteration and aggregation/fibrillation under both thermal and thermochemical systems. The conformational stability of lens crystallins was increased upon glycation, showing the reason behind resistance of glycated proteins against stress-induced structural alteration and aggregation. Due to the resistance of glycated lens crystallins against aggregation, the role of this modification in development of senile cataract can be explained with the associated damaging consequences highlighted in this article.
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
authors.affiliation: 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: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Amirghofran
authors.affiliation: Department of Pathology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Oryan
authors.affiliation: Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran.
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Moosavi-Movahedi
mesh_terms: D000818:Animals; D002386:Cataract / Q000209:etiology / Q000378:metabolism; D002417:Cattle; D003459:Crystallins / Q000737:chemistry* / Q000378:metabolism; D048909:Diabetes Complications; D006031:Glycosylation; D066329:Protein Aggregates; D055550:Protein Stability; D017382:Reactive Oxygen Species; D013057:Spectrum Analysis / Q000379:methods; D013312:Stress, Physiological; D038201:alpha-Crystallins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D003459:Crystallins; D066329:Protein Aggregates; D017382:Reactive Oxygen Species; D038201:alpha-Crystallins
keywords: Aggregation; Glycation; Lens crystalins