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JAK-STAT通路介导gx-50针对神经元的抗氧化保护作用的研究

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  • 上海交通大学 生命科学技术学院, 上海200240

作者简介: 陈祎(1991-), 女, 硕士生, 研究方向:分子生物学, E-mail:chenyi527@hotmail.com;

通讯作者: 乔中东(1957-), 男, 博士生导师, 教授, 研究方向:环境因素对细胞发育的影响, E-mail:zdqiao@sjtu.edu.cn

收稿日期: 2015-04-29

  网络出版日期: 2016-03-08

基金资助

国家自然科学基金(J1210047)

JAK-STAT Pathway Mediates Anti-Oxidative Effects of gx-50 on Neuron

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  • School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai 200240, China

Received date: 2015-04-29

  Online published: 2016-03-08

摘要

gx-50已被证明在阿尔茨海默症中具有神经保护作用, 然而其抗氧化机制在很大程度上仍然是未知的。为探究gx-50对在阿尔茨海默症中处于氧化应激状态的神经元细胞起到的保护作用, 本文通过测定细胞内活性氧(ROS)水平、细胞内总超氧化物歧化酶(SOD)活性和细胞分泌物丙二醛(MDA)含量检测gx-50在细胞水平的抗氧化能力。并检测了gx-50在细胞和组织水平对于JAK-STAT信号通路和caspase-3蛋白表达水平的影响。结果表明, gx-50可以使暴露于β淀粉样蛋白(Aβ)的PC12细胞分泌的ROS和MDA水平降低, 并保护胞内总SOD酶活性; gx-50可以在细胞和组织水平活化JAK-STAT信号通路, 可以降低PC12细胞内caspase-3蛋白活性亚基的相对表达水平; 而JAK2的特异性抑制剂, AG490, 逆转了gx-50的以上抗氧化保护作用。这表明gx-50可以通过活化JAK-STAT通路, 一定程度上减弱神经元所受到的氧化损伤, 对神经元起到保护作用, 因此在阿尔茨海默症预防治疗方面具有一定的应用前景。

本文引用格式

陈祎, 史诗, 梁冬丽, 王朝霞, 乔中东 . JAK-STAT通路介导gx-50针对神经元的抗氧化保护作用的研究[J]. 上海交通大学学报(农业科学版), 2016 , 34(1) : 16 -23 . DOI: 10.3969/J.ISSN.1671-9964.2016.01.004

Abstract

A novel compound derived from Zanthoxylum, gx-50(N-[2-(3, 4-dimethoxyphenyl)ethyl]-3-phenyl-acrylamide), has been demonstrated that it has neuroprotective effects against Alzheimer’s disease(AD)by our previous study.This study focuses on the mechanism of its antioxidant properties against AD.We measured the levels of intracellular reactive oxygen species(ROS), superoxide dismutase(SOD)activity and malondialdehyde(MDA)to determine the anti-oxidative ability of gx-50 at cellular level.We also measured gx-50’s effect on JAK-STAT signaling pathway and the relative expression levels of activated caspase-3.Data showed that gx-50 reduced the levels of reactive oxygen species(ROS)and malondialdehyde(MDA), and recovered the activity of total intracellular superoxide dismutase(SOD)in neuronal PC12 cells exposed to Aβ.After gx-50 pretreatment, the levels of p-JAK2 and p-STAT3 both increased in PC12 cells, while they were down-regulated in Aβ-treated group.In present study, we also found that gx-50 reduced the relative expression level of the activated caspase-3 in PC12 cells by activating JAK-STAT signaling pathway.Results demonstrated that gx-50 reduced amyloid-beta(Aβ)induced oxidative stress in neuron-like PC12 cells by enhancing the activation of JAK-STAT signaling pathway.It might help to protect neurons in Alzheimer's disease.

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