title: Advanced glycation end products induce differential structural modifications and fibrillation of albumin.
abstract: Glycation induced amyloid fibrillation is fundamental to the development of many neurodegenerative and cardiovascular complications. Excessive non-enzymatic glycation in conditions such as hyperglycaemia results in the increased accumulation of advanced glycation end products (AGEs). AGEs are highly reactive pro-oxidants, which can lead to the activation of inflammatory pathways and development of oxidative stress. Recently, the effect of non-enzymatic glycation on protein structure has been the major research area, but the role of specific AGEs in such structural alteration and induction of fibrillation remains undefined. In this study, we determined the specific AGEs mediated structural modifications in albumin mainly considering carboxymethyllysine (CML), carboxyethyllysine (CEL), and argpyrimidine (Arg-P) which are the major AGEs formed in the body. We studied the secondary structural changes based on circular dichroism (CD) and spectroscopic analysis. The AGEs induced fibrillation was determined by Congo red binding and examination of scanning and transmission electron micrographs. The amyloidogenic regions in the sequence of BSA were determined using FoldAmyloid. It was observed that CEL modification of BSA leads to the development of fibrillar structures, which was evident from both secondary structure changes and TEM analysis.
authors.affiliation: Molecular Biophysics Lab, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, Tamilnadu, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Awasthi
authors.affiliation: DST-INSPIRE Faculty, Department of Energy and Environment, National Institute of Technology, Tiruchirappalli 620015, Tamilnadu, India.
authors.forename: Kamatchi
authors.initials: K
authors.lastname: Sankaranarayanan
authors.affiliation: Molecular Biophysics Lab, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613401, Tamilnadu, India. Electronic address: saras@scbt.sastra.edu.
authors.forename: N T
authors.initials: NT
authors.lastname: Saraswathi
mesh_terms: D000682:Amyloid / Q000737:chemistry; D000818:Animals; D001120:Arginine / Q000378:metabolism; D002417:Cattle; D002942:Circular Dichroism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D008239:Lysine / Q000378:metabolism; D017433:Protein Structure, Secondary; D012710:Serum Albumin, Bovine / Q000737:chemistry* / Q000187:drug effects* / Q000648:ultrastructure; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000682:Amyloid; D017127:Glycation End Products, Advanced; D012710:Serum Albumin, Bovine; D001120:Arginine; D008239:Lysine
keywords: Albumin; Amyloid; Argpyrimidine; Carboxyethyllysine; Carboxymethyllysine; Fibrillation; Glycation