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In vitro toxicity and molecular interacting mechanisms of chloroacetic acid to catalase.
Ecotoxicology and Environmental Safety ( IF 6.2 ) Pub Date : 2019-12-04 , DOI: 10.1016/j.ecoenv.2019.109981 Jing Wang 1 , Hongfa Zhang 1 , Xiaolin Zheng 1 , Rutao Liu 2 , Wansong Zong 3
Ecotoxicology and Environmental Safety ( IF 6.2 ) Pub Date : 2019-12-04 , DOI: 10.1016/j.ecoenv.2019.109981 Jing Wang 1 , Hongfa Zhang 1 , Xiaolin Zheng 1 , Rutao Liu 2 , Wansong Zong 3
Affiliation
Chloroacetic acid (CAA), one of typical disinfection by-products (DBPs), has attracted considerable concerns for its biological safety. Antioxidant enzyme catalase (CAT) plays a crucial part in the regulation of redox state balance. Herein, CAA was used to test its adverse effects on CAT and explore the underlying mechanism. The cell viability of mouse primary hepatocytes decreased under CAA exposure. A bell-shaped response to CAA exposure was observed in intracellular CAT activity, whose change was partly influenced by molecular CAT activity. CAA binds to CAT mainly via van der Waals forces and hydrogen bonds with a stoichiometry of 9.2. The binding caused structural changes in CAT with the unfolding of polypeptide chains and the decrease of α-helical content. CAA interacts with the amino acid residues surrounding the active sites and substrate channel of CAT. These interactions result in the decrease of molecular CAT activity, which could be restored by high ionic strength. This study has provided a combined molecular and cellular tactics for studying the adverse effects of DBPs on biomarkers and the underlying mechanisms.
中文翻译:
氯乙酸对过氧化氢酶的体外毒性和分子相互作用机理。
氯乙酸(CAA)是一种典型的消毒副产物(DBP),对其生物安全性引起了极大的关注。抗氧化酶过氧化氢酶(CAT)在氧化还原状态平衡的调节中起着至关重要的作用。本文中,CAA用于测试其对CAT的不利影响并探索其潜在机制。在CAA暴露下,小鼠原代肝细胞的细胞活力下降。在细胞内CAT活性中观察到对CAA暴露的钟形响应,其变化部分受到分子CAT活性的影响。CAA主要通过范德华力和氢键与CAT结合,化学计量比为9.2。随着多肽链的展开和α-螺旋含量的减少,结合引起CAT的结构变化。CAA与CAT的活性位点和底物通道周围的氨基酸残基相互作用。这些相互作用导致分子CAT活性的降低,可以通过高离子强度来恢复。这项研究提供了结合分子和细胞策略,以研究DBP对生物标志物的不利影响及其潜在机制。
更新日期:2019-12-04
中文翻译:
氯乙酸对过氧化氢酶的体外毒性和分子相互作用机理。
氯乙酸(CAA)是一种典型的消毒副产物(DBP),对其生物安全性引起了极大的关注。抗氧化酶过氧化氢酶(CAT)在氧化还原状态平衡的调节中起着至关重要的作用。本文中,CAA用于测试其对CAT的不利影响并探索其潜在机制。在CAA暴露下,小鼠原代肝细胞的细胞活力下降。在细胞内CAT活性中观察到对CAA暴露的钟形响应,其变化部分受到分子CAT活性的影响。CAA主要通过范德华力和氢键与CAT结合,化学计量比为9.2。随着多肽链的展开和α-螺旋含量的减少,结合引起CAT的结构变化。CAA与CAT的活性位点和底物通道周围的氨基酸残基相互作用。这些相互作用导致分子CAT活性的降低,可以通过高离子强度来恢复。这项研究提供了结合分子和细胞策略,以研究DBP对生物标志物的不利影响及其潜在机制。