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植物激素脱落酸通过其抗氧化和抗凋亡特性保护人神经母细胞瘤 SH-SY5Y 细胞免受 6-羟多巴胺诱导的神经毒性。

Phytohormone Abscisic Acid Protects Human Neuroblastoma SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Neurotoxicity Through Its Antioxidant and Antiapoptotic Properties.

机构信息

1 Department of Biology, Rasht Branch, Islamic Azad University. Rasht, Iran.

2 Laboratory of Molecular Neuroscience, Kerman Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Rejuvenation Res. 2019 Apr;22(2):99-108. doi: 10.1089/rej.2018.2062. Epub 2018 Oct 6.

Abstract

Parkinson's disease (PD) is a destroying and prevalent neurodegenerative disease that is characterized by a progressive death of midbrain dopaminergic neurons. It is important to understand the possible neuroprotective effects of reagents that rescue the neurons from death and apoptosis. In this study, we investigated the effects of abscisic acid (ABA) on 6-hydroxydopamine (6-OHDA)-induced neurotoxicity in human dopaminergic neuroblastoma SH-SY5Y cell line as an model of PD. Cell damage was induced by 150 μM 6-OHDA and the cell viability was examined by 2-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and mitochondrial membrane potential were assessed by fluorescence probe methods. Biochemical markers of apoptosis were also determined by immunoblotting. The data showed that 6-OHDA caused a significant loss of cell viability and mitochondrial membrane potential. In addition, intracellular ROS, cleaved caspase-3, Bax:Bcl-2 ratio, and cytochrome c release were significantly increased in 6-OHDA-incubated cells. ABA (100 μM) elicited a significant protective effect and reduced biochemical markers of cell damage and death. Blockage of peroxisome proliferator-activated receptor (PPAR)γ completely prevented the effect of ABA on 6-OHDA-induced cell toxicity. The results suggest that ABA has neuroprotective property against 6-OHDA-induced neurotoxicity, which is performed through PPARγ signaling. However, ABA antioxidant and antiapoptotic properties are involved, at least in part, in such protection.

摘要

帕金森病(PD)是一种破坏性和普遍的神经退行性疾病,其特征是中脑多巴胺能神经元进行性死亡。了解能够挽救神经元免于死亡和凋亡的试剂的可能神经保护作用非常重要。在这项研究中,我们研究了脱落酸(ABA)对人多巴胺能神经母细胞瘤 SH-SY5Y 细胞系中 6-羟多巴胺(6-OHDA)诱导的神经毒性的影响,作为 PD 的模型。通过 150 μM 6-OHDA 诱导细胞损伤,并通过 2-[4,5-二甲基-2-噻唑基]-2,5-二苯基-2-四唑溴盐(MTT)测定法检查细胞活力。通过荧光探针法评估活性氧(ROS)和线粒体膜电位。还通过免疫印迹法测定凋亡的生化标志物。数据表明,6-OHDA 导致细胞活力和线粒体膜电位显著丧失。此外,6-OHDA 孵育的细胞中细胞内 ROS、裂解的 caspase-3、Bax:Bcl-2 比值和细胞色素 c 释放明显增加。ABA(100 μM)产生了显著的保护作用,并降低了细胞损伤和死亡的生化标志物。过氧化物酶体增殖物激活受体(PPAR)γ 的阻断完全阻止了 ABA 对 6-OHDA 诱导的细胞毒性的影响。结果表明,ABA 对 6-OHDA 诱导的神经毒性具有神经保护作用,这是通过 PPARγ 信号转导实现的。然而,ABA 的抗氧化和抗凋亡特性至少部分参与了这种保护。

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