title: Glyoxal induced structural transition of buffalo kidney cystatin to molten globule and aggregates: Anti-fibrillation potency of quinic acid.
abstract: In our study buffalo kidney cystatin (BKC) is transformed from native conformation to amyloid fibrils when incubated with 20 mM glyoxal for a prolonged time period. These amyloid fibrils are at the heart of a number of pathological disorders. In the presence of 10 mM glyoxal, BKC retained native-like secondary structure, decreased intrinsic and increased ANS fluorescence was observed, characteristics of molten globule state (MG), thus suggesting the occurrence of MG state at this concentration. At 20 mM glyoxal, BKC aggregates were characterized by a further decrease in ANS fluorescence attributable to internalization of hydrophobic clusters owing to protein-protein interaction. Circular dichroism and FTIR spectroscopy further revealed the existence of β sheet structure and there was an increase in Thioflavin T fluorescence, Rayleigh light scattering, turbidity as well as red shift in congo red absorbance thus confirming the existence of aggregates. We have also studied the anti-aggregation effect of polyol, quinic acid making use of various above mentioned biophysical assays. Our proposed work strongly favors the formation of BKC aggregates in the presence of glyoxal, which is present in higher amounts in pathological conditions owing to defective glycolysis pathway and also use of polyol as an antifibrillating agent.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors.forename: Anas
authors.initials: A
authors.lastname: Shamsi
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors.forename: Azaj
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
authors.forename: Bilqees
authors.initials: B
authors.lastname: Bano
mesh_terms: D000682:Amyloid / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002020:Buffaloes; D002942:Circular Dichroism; D015891:Cystatins / Q000378:metabolism; D006037:Glyoxal / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D066263:Protein Aggregation, Pathological / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017433:Protein Structure, Secondary / Q000187:drug effects; D011801:Quinic Acid / Q000008:administration & dosage*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D000682:Amyloid; D015891:Cystatins; D011801:Quinic Acid; D006037:Glyoxal
keywords: BKC aggregates; buffalo kidney cystatin; glyoxal; molten globule; quinic acid