| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1231360 | Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy | 2016 | 8 Pages |
•AGEs modification led to the secondary structural changes in BSA.•The analysis of BSA sequence showed the presence of amyloidogenic regions.•Formation of CEL-BSA exhibited formation of fibrillar aggregates.
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.
Graphical abstractAdvanced glycation modification mediated conformational transition of native helical BSA towards the beta sheeted unordered conformation.Figure optionsDownload full-size imageDownload as PowerPoint slide
