Analysis of the signal transduction pathway of the transcription factor NF-κB activated by cytokines

细胞因子激活转录因子NF-κB信号转导通路分析

基本信息

  • 批准号:
    13660083
  • 负责人:
  • 金额:
    $ 2.18万
  • 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:
    2001
  • 资助国家:
    日本
  • 起止时间:
    2001 至 2002
  • 项目状态:
    已结题

项目摘要

Acetoxycycloheximide (E-73) inhibits induction of the transcription factor NF-κB by TNF in the lung carcinoma A549 cells. Although E-73 failed to affect the expression of the adaptor proteins TRADD, RIP, and TRAF2, which are essential for activation of the NF-κB signaling pathway, the agent induced the downregulation of the cell-surface TNF receptor 1 via activation of p38 MAP kinase. By contrast, E-73 selectively induced caspase-dependent apoptosis and cytochrome c release from mitochondria in the human leukemia HL-60 and Jurkat T cells. E-73-induced cytochrome c release was blocked by the Bcl-2 family member Bcl-x_L and the JNK inhibitor SP600125, but was unaffected by the caspase inhibitor z-VAD-fmk and the p38 MAP kinase inhibitor SB203580. Thus, these data suggest that E-73 induces cytochrome c release from mitochondria through the JNK activation, thereby triggering the caspase cascade.The mycotoxin penicillic acid inhibited apoptosis by preventing activation of caspase-8, but not recruitment of caspase-8 into the Fas-FADD complex upon stimulation with Fas ligand (FasL). Penicillic acid inhibited the enzymatic activities of caspase-3, caspase-8, and casoase-9. However, penicillic acid weakly inhibited activation of caspase-3 and casoase-9 in staurosporine-treated cells, but did inhibit caspase-8 activation in FasL-treated cells, suggesting that penicillic acid selectively targets caspase-8 at the cellular level. Glutathione and cysteine suppressed the inhibitory effect of penicillic acid on caspase-8, and penicillic acid directly bound to the active center cysteine of caspase-8. These results demonstrate that penicillic acid inhibits FasL-induced apoptosis by blocking the self-processing of caspase-8.
Acetoxycycloheximide (E-73)抑制TNF对肺癌A549细胞转录因子NF-κB的诱导作用。虽然E-73不能影响NF-κB信号通路激活所必需的接头蛋白TRADD、RIP和TRAF2的表达,但该药物通过激活p38 MAP激酶诱导细胞表面TNF受体1的下调。相比之下,E-73选择性诱导人白血病HL-60和Jurkat T细胞的caspase依赖性凋亡和线粒体细胞色素c释放。e -73诱导的细胞色素c释放被Bcl-2家族成员Bcl-x_L和JNK抑制剂SP600125阻断,但不受caspase抑制剂z-VAD-fmk和p38 MAP激酶抑制剂SB203580的影响。因此,这些数据表明E-73通过JNK激活诱导线粒体释放细胞色素c,从而触发caspase级联反应。霉菌毒素青霉素酸通过阻止caspase-8的激活来抑制细胞凋亡,但在Fas配体(FasL)刺激下,caspase-8不被募集到Fas- fadd复合体中。青霉素酸抑制caspase-3、caspase-8和cascasase -9的酶活性。然而,在staurosporine处理的细胞中,青霉素酸弱抑制caspase-3和cascasase -9的激活,但在fasl处理的细胞中却抑制caspase-8的激活,这表明青霉素酸在细胞水平上选择性地靶向caspase-8。谷胱甘肽和半胱氨酸抑制了青霉酸对caspase-8的抑制作用,青霉酸直接与caspase-8的活性中心半胱氨酸结合。这些结果表明,青霉素酸通过阻断caspase-8的自我加工来抑制fasl诱导的细胞凋亡。

项目成果

期刊论文数量(27)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yasunobu Miyake: "Epoxycyclohexenone inhibits Fas-mediated apoptosis by blocking activation of pro-caspase-8 in the death-inducing signaling complex"Journal of Biological Chemistry. 278 (13). 11213-11220 (2003)
Yasunobu Miyake:“环氧环己烯酮通过阻断死亡诱导信号复合物中 caspase-8 前体的激活来抑制 Fas 介导的细胞凋亡”《生物化学杂志》。
  • DOI:
  • 发表时间:
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  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yasunobu Miyake: "Epoxycyclohexenone inhibits Fas-mediated apoptosis by blocking activation of pro-caspase-8 in the death-inducing signaling complex"Journal of Biological Chemistry. 278(13). 11213-11220 (2003)
Yasunobu Miyake:“环氧环己烯酮通过阻断死亡诱导信号复合物中 caspase-8 前体的激活来抑制 Fas 介导的细胞凋亡”《生物化学杂志》。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
片岡 孝夫: "T細胞による細胞殺傷機能発現の制御機構に関する研究"日本農芸化学会誌. 76. 922-929 (2002)
Takao Kataoka:“T细胞表达细胞杀伤功能的控制机制的研究”日本农业化学学会杂志76. 922-929(2002)。
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
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  • 通讯作者:
Takao Kataoka: "Molecular Anatomy of Cellular Systems"Elsevier Science B.V.. 11 (2002)
Takao Kataoka:“细胞系统的分子解剖学”Elsevier Science B.V.. 11 (2002)
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Izuru Ando: "Safflower polysaccharides activate the transcription factor NF-κB via Toll-like receptor 4 and induce cytokine production by macrophages"International Immunopharmacology. 2. 1155-1162 (2002)
Izuru Ando:“红花多糖通过 Toll 样受体 4 激活转录因子 NF-κB,并诱导巨噬细胞产生细胞因子”国际免疫药理学 2. 1155-1162 (2002)。
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  • 影响因子:
    0
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KATAOKA Takao其他文献

KATAOKA Takao的其他文献

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{{ truncateString('KATAOKA Takao', 18)}}的其他基金

Construction of membrane-bound hybrid molecules for analyzing cytotoxic granules
用于分析细胞毒性颗粒的膜结合杂化分子的构建
  • 批准号:
    21K19080
  • 财政年份:
    2021
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Challenging Research (Exploratory)
Elucidation of molecular mechanisms of bioprobes on signaling pathways of inflammatory responses and hypoxic responses
阐明生物探针对炎症反应和缺氧反应信号通路的分子机制
  • 批准号:
    16H04910
  • 财政年份:
    2016
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular mechanisms of signaling pathways regulating inflammatory responses and their elucidation by bioprobes
调节炎症反应的信号通路的分子机制及其生物探针的阐明
  • 批准号:
    25292061
  • 财政年份:
    2013
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Molecular mechanism of inflammatory cytokine signaling and its regulation by bioprobes
炎症细胞因子信号传导的分子机制及其生物探针的调控
  • 批准号:
    22380060
  • 财政年份:
    2010
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Development of functional analysis of secretory lysosomes
分泌型溶酶体功能分析的进展
  • 批准号:
    22658036
  • 财政年份:
    2010
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Molecular mechanism and bioprobes of cytokine receptor signaling
细胞因子受体信号传导的分子机制和生物探针
  • 批准号:
    19380057
  • 财政年份:
    2007
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of molecular mechanism of signal transduction pathway via cytokine receptors by bioprobes
生物探针分析细胞因子受体信号转导途径的分子机制
  • 批准号:
    15380069
  • 财政年份:
    2003
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Analysis of apoptosis induction and NF-κB activation mediated by death receptors
死亡受体介导的细胞凋亡诱导和 NF-κB 激活分析
  • 批准号:
    11660077
  • 财政年份:
    1999
  • 资助金额:
    $ 2.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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Cycloheximide-resicetance gene isolated from Candida maltosa : Mechanism of action and its utilization
麦芽糖念珠菌中分离的放线菌酮抗性基因:作用机制及其利用
  • 批准号:
    61470129
  • 财政年份:
    1986
  • 资助金额:
    $ 2.18万
  • 项目类别:
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