In vitro modelling of Parkinson's disease using 6-OHDA is associated with increased NQO2 activity

IF 2.6 3区医学 Q3 TOXICOLOGY

Toxicology in Vitro Pub Date : 2024-09-11 DOI:10.1016/j.tiv.2024.105940

Ekaterina R. Verbovaya , Ilya A. Kadnikov , Ilya O. Logvinov , Tatyana A. Antipova , Mikhail V. Voronin , Sergei B. Seredenin

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Abstract

The pathogenesis of Parkinson's disease (PD) involves abnormalities in the metabolism of catecholamines. The enzyme quinone reductase 2 (NQO2) reduces quinone derivatives of catecholamines, which promotes the formation of reactive oxygen species (ROS), suggesting a role for NQO2 in the development of cellular damage typical of PD. In the present study, we investigated the relationship between 6-hydroxydophamine (6-OHDA) induced cellular damage and NQO2 activity and its levels in SH-SY5Y cell culture to establish an experimental model to evaluate the pharmacological properties of NQO2 inhibitors. Cellular damage was evaluated using the MTT and comet assays. It was shown that oxidative damage of SH-SY5Y cells upon incubation with 6-OHDA for 6, 12 and 24 h was accompanied by an increase in NQO2 activity. The increase in NQO2 protein level in SH-SY5Y cells was observed 24 h after incubation with 6-OHDA at concentrations of 50 and 100 μM. Oxidative damage of SH-SY5Y cells upon 1 h incubation with 6-OHDA is increased in the presence of the selective enzyme co-substrate 1-benzyl-1,4-dihydronicotinamide (BNAH), but is not accompanied by changes in NQO2 activity and protein levels. The data obtained demonstrate the contribution of NQO2 to the cytotoxic mechanism of 6-OHDA action.

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使用 6-OHDA 在体外模拟帕金森病与 NQO2 活性增加有关

帕金森病（PD）的发病机制涉及儿茶酚胺代谢异常。醌还原酶 2（NQO2）可还原儿茶酚胺的醌衍生物，从而促进活性氧（ROS）的形成，这表明 NQO2 在帕金森病典型的细胞损伤发展过程中发挥作用。在本研究中，我们研究了 6-羟基多巴胺（6-OHDA）诱导的细胞损伤与 SH-SY5Y 细胞培养中 NQO2 活性及其水平之间的关系，从而建立一个实验模型来评估 NQO2 抑制剂的药理特性。细胞损伤采用 MTT 和彗星试验进行评估。结果表明，6-OHDA 培养 6、12 和 24 小时后，SH-SY5Y 细胞的氧化损伤伴随着 NQO2 活性的增加。用浓度为 50 和 100 μM 的 6-OHDA 培养 24 小时后，观察到 SH-SY5Y 细胞中 NQO2 蛋白水平的增加。在选择性酶辅助底物 1-苄基-1,4-二氢烟酰胺（BNAH）存在的情况下，SH-SY5Y 细胞在与 6-OHDA 培养 1 小时后的氧化损伤增加，但 NQO2 活性和蛋白水平没有发生变化。所获得的数据证明了 NQO2 对 6-OHDA 的细胞毒性作用机制的贡献。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Toxicology in Vitro 医学-毒理学

CiteScore

6.50

自引率

3.10%

发文量

181

审稿时长

65 days

期刊介绍： Toxicology in Vitro publishes original research papers and reviews on the application and use of in vitro systems for assessing or predicting the toxic effects of chemicals and elucidating their mechanisms of action. These in vitro techniques include utilizing cell or tissue cultures, isolated cells, tissue slices, subcellular fractions, transgenic cell cultures, and cells from transgenic organisms, as well as in silico modelling. The Journal will focus on investigations that involve the development and validation of new in vitro methods, e.g. for prediction of toxic effects based on traditional and in silico modelling; on the use of methods in high-throughput toxicology and pharmacology; elucidation of mechanisms of toxic action; the application of genomics, transcriptomics and proteomics in toxicology, as well as on comparative studies that characterise the relationship between in vitro and in vivo findings. The Journal strongly encourages the submission of manuscripts that focus on the development of in vitro methods, their practical applications and regulatory use (e.g. in the areas of food components cosmetics, pharmaceuticals, pesticides, and industrial chemicals). Toxicology in Vitro discourages papers that record reporting on toxicological effects from materials, such as plant extracts or herbal medicines, that have not been chemically characterized.