Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase

IF 2.8 4区医学 Q2 TOXICOLOGY Toxicology Mechanisms and Methods Pub Date : 2017-01-02 DOI:10.3109/15376516.2016.1172691

Lei Bao, J. Zu, Qian-qian He, Hui Zhao, Su Zhou, X. Ye, Xinxin Yang, Kun Zan, Zuohui Zhang, Hongjuan Shi, G. Cui

{"title":"Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase","authors":"Lei Bao, J. Zu, Qian-qian He, Hui Zhao, Su Zhou, X. Ye, Xinxin Yang, Kun Zan, Zuohui Zhang, Hongjuan Shi, G. Cui","doi":"10.3109/15376516.2016.1172691","DOIUrl":null,"url":null,"abstract":"Abstract Context: Studies have shown that thrombin activation played a central role in cell injuries associated with intracerebral hemorrhage (ICH). Objective: Here, our study investigated the cytotoxicity of thrombin on neurons, and determined the involvement of JNK pathways in thrombin-induced neuronal apoptosis. Materials and methods: Primary cultured neurons were treated with different doses of thrombin. Some neurons were given either SP600125 or vehicle. LDH release assay and flow cytometry were used to measure neuronal apoptosis caused by thrombin. The activation of JNK and capases-3 were measured by Western blot. Results: Our results showed large doses of thrombin that increased the LDH release, the level of cleaved caspase-3 and apoptosis rate of neurons. JNK was activated by thrombin in a time-dependent manner. Administration of SP600125 protects neurons from thrombin-induced apoptosis. Conclusion: These data indicate that the activation of JNK is crucial for thrombin-induced neuronal apoptosis, and inhibition of JNK may be a potential therapeutic target for ICH.","PeriodicalId":49117,"journal":{"name":"Toxicology Mechanisms and Methods","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2017-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/15376516.2016.1172691","citationCount":"7","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology Mechanisms and Methods","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3109/15376516.2016.1172691","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"TOXICOLOGY","Score":null,"Total":0}

引用次数: 7

Abstract

Abstract Context: Studies have shown that thrombin activation played a central role in cell injuries associated with intracerebral hemorrhage (ICH). Objective: Here, our study investigated the cytotoxicity of thrombin on neurons, and determined the involvement of JNK pathways in thrombin-induced neuronal apoptosis. Materials and methods: Primary cultured neurons were treated with different doses of thrombin. Some neurons were given either SP600125 or vehicle. LDH release assay and flow cytometry were used to measure neuronal apoptosis caused by thrombin. The activation of JNK and capases-3 were measured by Western blot. Results: Our results showed large doses of thrombin that increased the LDH release, the level of cleaved caspase-3 and apoptosis rate of neurons. JNK was activated by thrombin in a time-dependent manner. Administration of SP600125 protects neurons from thrombin-induced apoptosis. Conclusion: These data indicate that the activation of JNK is crucial for thrombin-induced neuronal apoptosis, and inhibition of JNK may be a potential therapeutic target for ICH.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

凝血酶通过激活c-Jun-N末端激酶诱导神经元凋亡

背景:研究表明凝血酶激活在脑出血(ICH)相关细胞损伤中起核心作用。目的:本研究探讨凝血酶对神经元的细胞毒性，并确定JNK通路在凝血酶诱导的神经元凋亡中的作用。材料与方法:用不同剂量凝血酶处理原代培养的神经元。部分神经元给予SP600125或载药。采用LDH释放法和流式细胞术检测凝血酶引起的神经元凋亡。Western blot检测JNK和capase -3的激活情况。结果:大剂量凝血酶可增加LDH的释放，增加裂解型caspase-3的水平，增加神经元的凋亡率。JNK被凝血酶以时间依赖性的方式激活。SP600125对凝血酶诱导的神经元凋亡具有保护作用。结论:这些数据表明，JNK的激活对凝血酶诱导的神经元凋亡至关重要，抑制JNK可能是脑出血的潜在治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Toxicology Mechanisms and Methods TOXICOLOGY-

自引率

3.10%

发文量

期刊介绍： Toxicology Mechanisms and Methods is a peer-reviewed journal whose aim is twofold. Firstly, the journal contains original research on subjects dealing with the mechanisms by which foreign chemicals cause toxic tissue injury. Chemical substances of interest include industrial compounds, environmental pollutants, hazardous wastes, drugs, pesticides, and chemical warfare agents. The scope of the journal spans from molecular and cellular mechanisms of action to the consideration of mechanistic evidence in establishing regulatory policy. Secondly, the journal addresses aspects of the development, validation, and application of new and existing laboratory methods, techniques, and equipment. A variety of research methods are discussed, including: In vivo studies with standard and alternative species In vitro studies and alternative methodologies Molecular, biochemical, and cellular techniques Pharmacokinetics and pharmacodynamics Mathematical modeling and computer programs Forensic analyses Risk assessment Data collection and analysis.