Modulation of apoptosis by activation of protein kinasse G

通过激活蛋白激酶 G 调节细胞凋亡

基本信息

  • 批准号:
    15590082
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

We investigated the protective effect of nitric oxide (NO) at a low concentration on NO- and hydrogen peroxide-induced cell death and its mechanism in mouse macrophage cell line, RAW264.SNP induced cell death in RAW264 cells at a high concentration (4 mM). Pretreatment with 100 μM SNP or 1 mM dibutylyl-cGMP reduced cytochrome c release from mitochondria and prevented the cell death induced by 4 mM SNP in RAW264 cells. The effect of SNP pretreatment was reduced by LY83583. Pretreatment with dibutylyl-cGMP prevented cell death induced by NOC 18, GSNO or SNP, in a concentration- dependent manner. Pretreatment with dibutylyl-cGMP prevented cytochrome c release induced by NO donors. The protective effect of SNP or dibutylyl-cGMP was significantly attenuated by KT5823 (a protein kinase G inhibitor). These results indicate that NO at a low concentration protects RAW264 cells from the cytotoxicity of NO through cGMP production and activation of PKG.Translocation of Bax from cytosol to mitochon … More dria was observed in the cell death. Untreated RAW264 cells displayed no Bax N-20 antibody (pAb raised against amino acids 11-30 of Bax)-associated immunoreactivity. However, some cells displayed a punctate cytosolic pattern of Bax immunostaining after 4 mM SNP treatment. Bax positive cells displayed a diffuse cytosolic pattern of cytochrome c immunostaining. The number of Bax positive cell was increased after 4 mM SNP treatment. Translocation of Bax and the increase of Bax positive cells induced by 4 mM SNP were inhibited by pretreatment with 100 μM SNP or 1 mM dibutylyl-cGMP. Activation of p38 MAP kinase induced by SNP at a high concentration was prevented by pretreatment with SNP at a low concentration or dibutylyl-cGMP. These results indicate that NO/cGMP signaling pathway inhibits NO-induced apoptpsis of macrophages by suppressing p38 MAP kinase activation, which results in N-terminal conformational change and translocation of Bax.Pretreatment with SNP or 1-hydroxy-2-oxo-3,3-bis-(2-aminoethyl)-1-triazene (NOC18), at a low concentration for 24 h reduced the H_2O_2-induced cell death, caspase-3 activation and nuclear fragmentation. LY83583 and ODQ, soluble guanylate cyclase inhibitors, inhibited the protective effect of both SNP and NOC18 pretreatment. Protein kinase G inhibitor KT5823 also significantly reduced these cytoprotective effects. These results indicate that NO at a low concentration protects RAW264 cells from H_2O_2-induced apoptosis though cGMP production and activation of protein kinase G. Less
我们研究了低浓度一氧化氮(NO)对NO和过氧化氢诱导的小鼠巨噬细胞系RAW 264细胞死亡的保护作用及其机制。高浓度(4 mM)SNP诱导RAW 264细胞死亡。用100 μM SNP或1 mM dibutyl-cGMP预处理RAW 264细胞可减少线粒体释放细胞色素c,并阻止4 mM SNP诱导的细胞死亡。LY 83583可降低SNP预处理的作用。用二丁基-cGMP预处理以浓度依赖性方式防止由NOC 18、GSNO或SNP诱导的细胞死亡。用二丁酰-环鸟苷酸预处理可阻止NO供体诱导的细胞色素c释放。蛋白激酶G抑制剂KT 5823可明显减弱SNP或dibutyl-cGMP的保护作用。这些结果表明,低浓度的NO通过产生cGMP和激活PKG来保护RAW 264细胞免受NO的细胞毒性。 ...更多信息 在细胞死亡中观察到DRIA。未处理的RAW 264细胞未显示Bax N-20抗体(针对Bax的氨基酸11-30产生的pAb)相关的免疫反应性。然而,一些细胞在4 mM SNP处理后显示出Bax免疫染色的点状胞质模式。Bax阳性细胞呈弥漫性细胞色素c免疫染色。4 mM SNP处理后Bax阳性细胞数增加。用100 μM SNP或1 mM dibutyl-cGMP预处理可抑制4 mM SNP诱导的Bax易位和Bax阳性细胞的增加。高浓度SNP诱导的p38 MAP激酶激活可被低浓度SNP或二丁基cGMP预处理所阻止。这些结果表明,NO/cGMP信号通路通过抑制p38 MAP激酶的激活,从而导致N端构象改变和Bax的移位,抑制NO诱导的巨噬细胞凋亡。(2-氨乙基)-1-三氮烯(NOC 18)在低浓度下作用24 h,可减少H_2O_2诱导的细胞死亡、caspase-3激活和核碎裂。可溶性鸟苷酸环化酶抑制剂LY 83583和ODQ可抑制SNP和NOC 18预处理的保护作用。蛋白激酶G抑制剂KT 5823也显着降低这些细胞保护作用。提示低浓度NO通过产生cGMP和激活蛋白激酶G对H_2O_2诱导的RAW 264细胞凋亡具有保护作用。少

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

MAEDA Sadaaki其他文献

MAEDA Sadaaki的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('MAEDA Sadaaki', 18)}}的其他基金

Research on the apelin as a therapeutic target molecule in ischemic retinopathy using genetically modified animals
使用转基因动物进行 apelin 作为缺血性视网膜病变治疗靶分子的研究
  • 批准号:
    24590131
  • 财政年份:
    2012
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Research on the onset and progression of amyotrophic lateral sclerosis using genetically modified animals
使用转基因动物研究肌萎缩侧索硬化症的发病和进展
  • 批准号:
    21590110
  • 财政年份:
    2009
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Dual effect of nitric oxide on cell death : Induction and protection of apoptosis
一氧化氮对细胞死亡的双重作用:诱导和保护细胞凋亡
  • 批准号:
    13672314
  • 财政年份:
    2001
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Effects of nitric oxide on pain perception by primary afferent neurons in inflammation
一氧化氮对炎症中初级传入神经元疼痛感知的影响
  • 批准号:
    11671840
  • 财政年份:
    1999
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Regulation of beta-agonist-induced secretion of amylase from rat parotid acini by K^+-channels
K^-通道调节β-激动剂诱导的大鼠腮腺腺泡淀粉酶分泌
  • 批准号:
    09671891
  • 财政年份:
    1997
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
MODULATION OF FACIAL AND DENTAL PAIN TRANSMISSION BY ENKEPHALIN IN TRIGEMINAL GANGLION
三叉神经节中脑啡肽对面部和牙齿疼痛传递的调节
  • 批准号:
    03670866
  • 财政年份:
    1991
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (C)

相似国自然基金

Epac1/2通过蛋白酶体调控中性粒细胞NETosis和Apoptosis在急性肺损伤中的作用研究
  • 批准号:
    LBY21H010001
  • 批准年份:
    2020
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
基于Apoptosis/Ferroptosis双重激活效应的天然产物AlbiziabiosideA的抗肿瘤作用机制研究及其结构改造
  • 批准号:
    81703335
  • 批准年份:
    2017
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目
双肝移植后Apoptosis和pyroptosis在移植物萎缩差异中的作用和供受者免疫微环境变化研究
  • 批准号:
    81670594
  • 批准年份:
    2016
  • 资助金额:
    58.0 万元
  • 项目类别:
    面上项目
Serp-2 调控apoptosis和pyroptosis 对肝脏缺血再灌注损伤的保护作用研究
  • 批准号:
    81470791
  • 批准年份:
    2014
  • 资助金额:
    73.0 万元
  • 项目类别:
    面上项目
Apoptosis signal-regulating kinase 1是七氟烷抑制小胶质细胞活化的关键分子靶点?
  • 批准号:
    81301123
  • 批准年份:
    2013
  • 资助金额:
    23.0 万元
  • 项目类别:
    青年科学基金项目
APO-miR(multi-targeting apoptosis-regulatory miRNA)在前列腺癌中的表达和作用
  • 批准号:
    81101529
  • 批准年份:
    2011
  • 资助金额:
    22.0 万元
  • 项目类别:
    青年科学基金项目
放疗与细胞程序性死亡(APOPTOSIS)相关性及其应用研究
  • 批准号:
    39500043
  • 批准年份:
    1995
  • 资助金额:
    9.0 万元
  • 项目类别:
    青年科学基金项目

相似海外基金

Milk fat globule-EGF factor 8 and hepatocyte apoptosis-induced liver wound healing response
乳脂肪球-EGF因子8与肝细胞凋亡诱导的肝脏创面愈合反应
  • 批准号:
    10585802
  • 财政年份:
    2023
  • 资助金额:
    $ 2.3万
  • 项目类别:
Development of an apoptosis biosensor for monitoring of breast cancer
开发用于监测乳腺癌的细胞凋亡生物传感器
  • 批准号:
    10719415
  • 财政年份:
    2023
  • 资助金额:
    $ 2.3万
  • 项目类别:
Interrogating the Fgl2-FcγRIIB axis on CD8+ T cells: A novel mechanism mediating apoptosis of tumor-specific memory CD8+ T cells
询问 CD8 T 细胞上的 Fgl2-FcγRIIB 轴:介导肿瘤特异性记忆 CD8 T 细胞凋亡的新机制
  • 批准号:
    10605856
  • 财政年份:
    2023
  • 资助金额:
    $ 2.3万
  • 项目类别:
Novel targeted therapy for FGFR inhibitor-resistant urothelial cancer and apoptosis based therapy for urothelial cancer
FGFR抑制剂耐药性尿路上皮癌的新型靶向治疗和基于细胞凋亡的尿路上皮癌治疗
  • 批准号:
    23K08773
  • 财政年份:
    2023
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Mechanistic analysis of apoptosis induction by HDAC inhibitors in head and neck cancer
HDAC抑制剂诱导头颈癌凋亡的机制分析
  • 批准号:
    23K15866
  • 财政年份:
    2023
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
Interrogating the Fgl2-FcgRIIB axis: A novel mechanism mediating apoptosis of tumor-specific memory CD8+ T cells
探究 Fgl2-FcgRIIB 轴:介导肿瘤特异性记忆 CD8 T 细胞凋亡的新机制
  • 批准号:
    10743485
  • 财政年份:
    2023
  • 资助金额:
    $ 2.3万
  • 项目类别:
Investigating the role of apoptosis-resistance and the tumor environment on development and maintenance of sacrococcygeal teratomas
研究细胞凋亡抗性和肿瘤环境对骶尾部畸胎瘤发生和维持的作用
  • 批准号:
    10749797
  • 财政年份:
    2023
  • 资助金额:
    $ 2.3万
  • 项目类别:
The effects of glucose on immune cell apoptosis and mitochondrial membrane potential and the analysis of its mechanism by which glucose might modulate the immune functions.
葡萄糖对免疫细胞凋亡和线粒体膜电位的影响及其调节免疫功能的机制分析。
  • 批准号:
    22K09076
  • 财政年份:
    2022
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
XAF1 IN P53 SIGNALING, APOPTOSIS AND TUMOR SUPPRESSION
P53 信号传导、细胞凋亡和肿瘤抑制中的 XAF1
  • 批准号:
    10583516
  • 财政年份:
    2022
  • 资助金额:
    $ 2.3万
  • 项目类别:
Role of Thioredoxin system in regulation of autophagy-apoptosis cross talk in neurons: Uncovering Novel Molecular Interactions.
硫氧还蛋白系统在神经元自噬-凋亡串扰调节中的作用:揭示新的分子相互作用。
  • 批准号:
    RGPIN-2019-05371
  • 财政年份:
    2022
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Discovery Grants Program - Individual
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了