Journal
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Volume 39, Issue 3, Pages 777-786Publisher
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2020.1715838
Keywords
Advanced glycation end product; Amyloid; HSA; Methylglyoxal; Quercetin
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Funding
- deanship of Scientific Research, Chair for Protein research, King Saud University, Riyadh, Saudi Arabia
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Methylglyoxal (MG) is a potent glycating agent that leads to conformational changes in HSA and amyloid formation, which can be inhibited by quercetin. The study demonstrates that quercetin effectively reverses the adverse effects of MG by sterically inhibiting the interaction between HSA and MG.
Methylglyoxal (MG) is a potent glycating agent which reacts with proteins to form advanced glycation end products (AGEs). These chemically stable AGEs crosslink with proteins and could lead to amyloid formation that has the role in several diseases including Alzheimer's and Parkinson's. In this piece of work, glycation-induced conformational changes in HSA were observed with quenching of tryptophan fluorescence by 73.8% (41 nm red shift) and loss of hydrophobicity of HSA. CD spectroscopy result reaffirmed secondary structure changes in HSA. Moreover, MG-induced changes in HSA, proceeds to amyloid structure as characterized by an increase in thioflavin (ThT) fluorescence and transmission electron microscopy (TEM) images of HSA aggregates. Quercetin was found to inhibit both AGEs production and amyloid formation. Viability of MCF-7 cells was found to be increased with AGEs treatment, illustrating proliferation of cancer cells. Wound healing assay also revealed increased proliferation and migration of cells in the presence of AGEs. Additionally, molecular docking analyses were performed to demonstrate interactions involved in the stabilization of HSA-quercetin complex. The binding affinities of quercetin were found to be (K-d = 10(5) M-1) much higher compared with MG (K-d = 10(2) M-1). From this study, it is quite clear that quercetin reverses the effect of MG by sterically inhibiting the interaction between HSA and MG. Communicated by Ramaswamy H. Sarma
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