Rescue of Neuronal Cell Death by ER-stress protein overexpression

通过 ER 应激蛋白过度表达拯救神经元细胞死亡

基本信息

项目摘要

ORP150 is a novel stress protein localized in the endoplasmic reticulum (ER). To investigate the role of ORP150 in delayed neuronal cell death, we have examined its expression in the gerbil brain after the ischemic insult. The expression of ORP150 antigen, as well as its transcripts, was observed in the CA1 region after the occlusion of the common carotid artery, and this was enhanced by the preconditioning. In cultured neurons, exposure to either hypoxia or glutamate induced the expression of ORP150, and this was also observed by treating the culture with either thapsigargin or breferdin-A, indicating that both glutamate and hypoxia can cause stress in the ER (ER stress). Neurons became more vulnerable to these stresses following treatment of either cycloheximide or the infection with an adenovirus carrying ORP150 antisense structure, In contrast, the overexpression of ORP150 by adenovirus suppressed the neuronal cell death, and this was accompanied by the suppression of the Ca2+ elev … More ation and proteolytic activity induced by glutamate. Further, overexpression of ORP150 in CA1 neurons by the adenovirus carrying ORP150-sense structure suppressed delayed neuronal cell death after ischemia. These date suggest a possible function of ORP150 as an intracellular apparatus, which participates in a protective response in ischemic tolerance.Selective loss of dopaminergic neurons is the final common pathway in Parkinson's disease. We discuss the role of ER-stress in neuronal cell death in SNpc by introducing two models. Upregulation of Pael-Receptor in the substantia nigra pars (SNpc) of mice induces endoplasmic reticulum (ER) stress leading to a decrease in tyrosine hydroxylase and death of dopaminergic neurons. The role of ER stress in dopaminergic neuronal vulnerability was highlighted by their enhanced death in mice deficient in the ubiquitin-protein ligase Parkin and the ER chaperone ORP150, suggesting parkin dysfunction result in ER-stress mediated neuronal cell death. Conversely, transgenic rats overexpressing megsin (Tg meg), a newly identified serine protease inhibitor (serpin), demonstrated intraneuronal periodic-acid Schiff (PAS) positive inclusions, which distributed throughout the deeper layers of cerebral cortex, hippocampal CA1, and substantia nigrta. Enhanced ER stress was observed in dopamine neurons in SNpc, accompanied with loss of neuronal viability and motor coordination. In both subregions, PAS-positive inclusions were also positive with megsin. These data suggest that enhanced ER stress causes selective vulnerability in a set of neuronal populations. Less
ORP 150是一种新的内质网应激蛋白。为了研究ORP 150在迟发性神经元细胞死亡中的作用,我们检测了其在缺血损伤后沙土鼠脑中的表达。ORP 150抗原的表达,以及它的转录本,在CA 1区观察后,闭塞的颈总动脉,这是增强的预处理。在培养的神经元中,暴露于缺氧或谷氨酸诱导ORP 150的表达,并且这也通过用毒胡萝卜素或breferdin-A处理培养物来观察,表明谷氨酸和缺氧都可以引起ER中的应激(ER应激)。神经元在放线菌酮处理或携带ORP 150反义结构的腺病毒感染后,对这些应激变得更脆弱。相反,由腺病毒过表达ORP 150抑制神经元细胞死亡,并且这伴随着Ca 2 + elevation的抑制。 ...更多信息 谷氨酸诱导的蛋白水解活性。此外,通过携带ORP 150正义结构的腺病毒在CA 1神经元中过表达ORP 150抑制缺血后的迟发性神经元细胞死亡。这些数据表明,ORP 150可能作为一个细胞内的装置,参与缺血耐受的保护性反应的功能。多巴胺能神经元的选择性损失是帕金森病的最终共同途径。我们通过介绍两种模型,讨论了内质网应激在SNPC神经细胞死亡中的作用。小鼠黑质部(SNpc)中Pael受体的上调诱导内质网(ER)应激,导致酪氨酸羟化酶减少和多巴胺能神经元死亡。ER应激在多巴胺能神经元脆弱性中的作用通过其在缺乏泛素蛋白连接酶Parkin和ER伴侣ORP 150的小鼠中的增强的死亡而突出,这表明Parkin功能障碍导致ER应激介导的神经元细胞死亡。相反,过表达megsin(Tg梅格),一种新发现的丝氨酸蛋白酶抑制剂(丝氨酸蛋白酶抑制剂)的转基因大鼠,表现出神经元内的α-酸性希夫(PAS)阳性夹杂物,分布在整个大脑皮层,海马CA 1区,和黑质的深层。在SNpc的多巴胺神经元中观察到增强的ER应激,伴随着神经元活力和运动协调的丧失。在这两个亚区,PAS阳性夹杂物也与megsin阳性。这些数据表明,增强ER应激导致一组神经元群体的选择性脆弱性。少

项目成果

期刊论文数量(42)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease.
  • DOI:
    10.1083/jcb.200108103
  • 发表时间:
    2002-06-24
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hori O;Ichinoda F;Tamatani T;Yamaguchi A;Sato N;Ozawa K;Kitao Y;Miyazaki M;Harding HP;Ron D;Tohyama M;M Stern D;Ogawa S
  • 通讯作者:
    Ogawa S
The ER chaperone 150 kDa Oxygen Regulated Protein (ORP150) improves insulin resistance in Type 2 Diabetes Mellitus.
ER 伴侣 150 kDa 氧调节蛋白 (ORP150) 可改善 2 型糖尿病的胰岛素抵抗。
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    小澤;小川;他
  • 通讯作者:
宮城 ほか: "Gene therapy for prostate cancer using the cytosine deaminase/uracil phosphoribosyltransferase suicide system"J Gene Med.. 5. 30-37 (2003)
Miyagi 等:“使用胞嘧啶脱氨酶/尿嘧啶磷酸核糖基转移酶自杀系统进行前列腺癌的基因治疗”J Gene Med.. 5. 30-37 (2003)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Accumulation of microglial cells expressing ELR motif-positive CXC chemokines and their receptors CXCR2 in monkey hippocanpus after ischemia-reperfusion.
缺血再灌注后猴海马中表达 ELR 基序阳性 CXC 趋化因子及其受体 CXCR2 的小胶质细胞的积累。
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Popivanova BK;Koike K;Tonchev AB;Ishida Y;Kondo T;Ogawa S;Mukaida N;Inoue M;Yamashima T.
  • 通讯作者:
    Yamashima T.
北尾 ほか: "ORP15O/HSP12A regulates purkinje cell survival : a role for ER stress in cerebellar development"J.Neurosci.. 24. 1486-1496 (2004)
Kitao 等人:“ORP15O/HSP12A 调节浦肯野细胞存活:ER 应激在小脑发育中的作用”J.Neurosci.. 24. 1486-1496 (2004)
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    0
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OGAWA Satoshi其他文献

Study on Evaluation Method of Slipperiness for Pets, Fundamental Study on Evaluation Method of Slipperiness
宠物防滑性评价方法研究、防滑性评价方法基础研究
The Adoption of the Latin American Rice Production System through the Implementation of Advanced Field Management Practices: An Evaluation of Technology Adoption Patterns and the Impact on Yield in Colombia
通过实施先进田间管理实践采用拉丁美洲水稻生产系统:技术采用模式及其对哥伦比亚产量影响的评估
  • DOI:
    10.5109/2558911
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    ALWARRITZI Widya;NANSEKI Teruaki;OGAWA Satoshi;LY Nguyen Thi;CHOMEI Yosuke;BECERRA Nilson Alfonso Ibarra;GALVIS Ricardo Andres Sanchez;GARC?A Myriam Patricia Guzm?n;VALBUENA Jose Levis Baron
  • 通讯作者:
    VALBUENA Jose Levis Baron

OGAWA Satoshi的其他文献

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{{ truncateString('OGAWA Satoshi', 18)}}的其他基金

Nano-interspace Modification of Organic Electronic Devices by Charge Transfer Type Self-assembled Monolayers
电荷转移型自组装单分子层对有机电子器件的纳米间隙修饰
  • 批准号:
    26410033
  • 财政年份:
    2014
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Control of Nano Interspace of Organic Electronic Devices by Charge Transfer Type Self-assembled Monolayers
电荷转移型自组装单分子层控制有机电子器件纳米间隙
  • 批准号:
    23550038
  • 财政年份:
    2011
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Design of Organic-Oraganometallic Hybrid Molecules with Mixed-valence Redox Activity
具有混合价氧化还原活性的有机-有机金属杂化分子的设计
  • 批准号:
    18550027
  • 财政年份:
    2006
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Design of Multi-center Multi-step Multi-redox Organic and Metallic Hybrid Molecules
多中心多步多氧化还原有机金属杂化分子的设计
  • 批准号:
    15550023
  • 财政年份:
    2003
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Experimental research for the availability of gene therapy using ORP150, a novel molecular chaperone
使用新型分子伴侣 ORP150 进行基因治疗可用性的实验研究
  • 批准号:
    12671522
  • 财政年份:
    2000
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
ESTABLISHMENT OF THE HEART FAILURE THERAPY USING REGENERATED CARDIOMYOCYTE FROM BONE MARROW
建立利用骨髓再生心肌细胞治疗心力衰竭的方法
  • 批准号:
    12307016
  • 财政年份:
    2000
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Visualization and regulation of ischemia-induced stress response in brain.
大脑缺血引起的应激反应的可视化和调节。
  • 批准号:
    10480215
  • 财政年份:
    1998
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B).
Morphological, Electrophysiological and Molecular Analysis of the Cardiomyocytes Defferentiated From Bone Marrow Mesenchymal Stem Cells
骨髓间充质干细胞分化心肌细胞的形态学、电生理学和分子分析
  • 批准号:
    10470170
  • 财政年份:
    1998
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Regulation of coronary circulation or pulmonary circulation in the setting of simulated space environments.
在模拟空间环境中调节冠脉循环或肺循环。
  • 批准号:
    05454276
  • 财政年份:
    1993
  • 资助金额:
    $ 28.87万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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GPR4 in blood brain barrier dysfunction in brain ischemia
GPR4在脑缺血血脑屏障功能障碍中的作用
  • 批准号:
    10711110
  • 财政年份:
    2022
  • 资助金额:
    $ 28.87万
  • 项目类别:
Change in NSF ATPase activity Leads to Brain Ischemia Reperfusion Injury
NSF ATP酶活性变化导致脑缺血再灌注损伤
  • 批准号:
    10748602
  • 财政年份:
    2022
  • 资助金额:
    $ 28.87万
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GPR4 in blood brain barrier dysfunction in brain ischemia
GPR4在脑缺血血脑屏障功能障碍中的作用
  • 批准号:
    10522141
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    2022
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    $ 28.87万
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Novel anti-NPC aggregation strategy against brain ischemia-reperfusion injury
抗脑缺血再灌注损伤的新型抗NPC聚集策略
  • 批准号:
    10747258
  • 财政年份:
    2022
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    $ 28.87万
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Metabolic origin of oxidative stress injury in brain ischemia/reperfusion
脑缺血/再灌注氧化应激损伤的代谢起源
  • 批准号:
    10354477
  • 财政年份:
    2022
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GPR4在脑缺血血脑屏障功能障碍中的作用
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    10652655
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    2022
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Metabolic Origin of Oxidative Stress Injury in Brain Ischemia/Reperfusion
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    10592282
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Association of brain temperature increase and cerebrospinal fluid dynamics in chronic brain ischemia due to main trunk occlusion of cerebral arteries
脑动脉主干闭塞所致慢性脑缺血脑温度升高与脑脊液动力学的关系
  • 批准号:
    21K09108
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    2021
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    $ 28.87万
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Neuroprotective role of OGR1 in brain ischemia
OGR1在脑缺血中的神经保护作用
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    10505248
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    2021
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Novel Ultrasound Indices of Intracranial Pressure and Brain Ischemia in Neonatal Hydrocephalus
新生儿脑积水颅内压和脑缺血的新型超声指标
  • 批准号:
    10455577
  • 财政年份:
    2020
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