The inhibitory effect and mechanism of small molecules on acetic anhydride-induced BSA acetylation and aggregation

乙酰化 醋酸酐 白藜芦醇 化学 没食子酸 芹菜素 小分子 生物化学 蛋白质聚集 荧光 抗氧化剂 类黄酮 量子力学 基因 物理 催化作用
作者
Xingli Huo,Huijun Liu,Shengjie Wang,Shanmei Yin,Zongning Yin
出处
期刊:Colloids and Surfaces B: Biointerfaces [Elsevier BV]
卷期号:225: 113265-113265 被引量:4
标识
DOI:10.1016/j.colsurfb.2023.113265
摘要

Protein acetylation is a significant post-translational modification, and hyperacetylation results in amyloid aggregation, which is closely related to neurodegenerative diseases (Alzheimer's disease, Huntington's disease, and so on). Therefore, it is significant to inhibit the hyperacetylation of proteins and their induced aggregation. In the present study, we aimed to explore the anti-acetylation and anti-amyloid properties of five small molecules (gallic acid, menadione, resveratrol, apigenin, and quercetin) in the process of acetic anhydride-induced protein hyperacetylation and its aggregation. Optical detection methods, such as SDS-PAGE, inverted fluorescence microscopy, and endogenous fluorescence spectroscopy, were used to investigate the effects of small molecules on protein acetylation, aggregation, and structure. In addition, fluorescence quenching and molecular docking techniques were used to explore the relationship between small molecules and acetylation. The results showed that gallic acid (200 μM), menadione (100 μM), quercetin (40 μM), resveratrol (5 μM), and apigenin (20 μM) (unmodified rates were 61.12 %, 67.76 %, 65.11 %, 62.66 %, and 67.81 %, respectively) had strong inhibitory effects on acetylation, and there was no significant difference (P < 0.05). In addition, gallic acid (200 μM), menadione (100 μM), and resveratrol (5 μM) (inhibition rates of 29.89 %, 26.53 %, and 26.09 %, respectively) had more substantial inhibitory effects on protein aggregation, indicating that the five small molecules could inhibit acetic anhydride-induced hyperacetylation and protein aggregation. The underlying mechanism might be that it could inhibit hyperacetylation and resist amyloid aggregation by interacting with proteins to occupy acetylation sites. Collectively, our findings showed that gallic acid, menadione, and resveratrol could potentially prevent and treat neurodegenerative diseases, such as Alzheimer's disease, by inhibiting acetylation and acetylation-induced aggregation.
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