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3-吡啶硼酸使鱼胚胎暴露于 1-甲基-4-苯基-1,2,3,6-四氢吡啶的影响正常化。

3-Pyridinylboronic acid normalizes the effects of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine exposure in zebrafish embryos.

机构信息

Faculty of Medicine, Department of Biophysics, Marmara University, Istanbul, Turkey.

Faculty of Dentistry, Department of Basic Medical Sciences, Marmara University, Istanbul, Turkey.

出版信息

Drug Chem Toxicol. 2022 Mar;45(2):947-954. doi: 10.1080/01480545.2020.1795189. Epub 2020 Jul 21.

Abstract

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that damages dopaminergic neurons. Zebrafish has been shown to be a suitable model organism to investigate the molecular pathways in the pathogenesis of Parkinson's disease and also for potential therapeutic agent research. Boron has been shown to play an important role in the neural activity of the brain. Boronic acids are used in combinatorial approaches in drug design and discovery. The effect of 3-pyridinylboronic acid which is an important sub-class of heterocyclic boronic acids has not been evaluated in case of MPTP exposure in zebrafish embryos. Accordingly, this study was designed to investigate the effects of 3-pyridinylboronic acid on MPTP exposed zebrafish embryos focusing on the molecular pathways related to neurodegeneration and apoptosis by RT-PCR. Zebrafish embryos were exposed to MPTP (800 μM); MPTP + Low Dose 3-Pyridinylboronic acid (50 μM) (MPTP + LB) and MPTP + High Dose 3-Pyridinylboronic acid (100 μM) (MPTP + HB) in well plates for 72 hours post fertilization. Results of our study showed that MPTP induced a P53 dependent and Bax mediated apoptosis in zebrafish embryos and 3-pyridinylboronic acid restored the locomotor activity and gene expressions related to mitochondrial dysfunction and oxidative stress due to the deleterious effects of MPTP, in a dose-dependent manner.

摘要

1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)是一种神经毒素,可损害多巴胺能神经元。斑马鱼已被证明是研究帕金森病发病机制中分子途径的合适模式生物,也可用于研究潜在的治疗药物。硼在大脑的神经活动中起着重要作用。硼酸用于药物设计和发现的组合方法中。3-吡啶硼酸作为杂环硼酸的重要亚类之一,其在 MPTP 暴露于斑马鱼胚胎中的作用尚未得到评估。因此,本研究旨在通过 RT-PCR 研究 3-吡啶硼酸对暴露于 MPTP 的斑马鱼胚胎的影响,重点研究与神经退行性变和细胞凋亡相关的分子途径。斑马鱼胚胎在受精后 72 小时内于培养板中暴露于 MPTP(800 μM);MPTP+低剂量 3-吡啶硼酸(50 μM)(MPTP+LB)和 MPTP+高剂量 3-吡啶硼酸(100 μM)(MPTP+HB)。我们的研究结果表明,MPTP 诱导斑马鱼胚胎中 P53 依赖性和 Bax 介导的细胞凋亡,3-吡啶硼酸以剂量依赖性方式恢复了由于 MPTP 的有害影响而导致的运动活性以及与线粒体功能障碍和氧化应激相关的基因表达。

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