The study on the glutamate-induced glial cell death mechanism for modulation of apoptosis to necrosis by arachidonic acid-mediated lipid peroxidation

花生四烯酸介导的脂质过氧化调控谷氨酸诱导胶质细胞凋亡至坏死的机制研究

基本信息

项目摘要

Glutamate induced glutathione (GSH) depletion leading to cell death in C6 rat glioma cells through accumulation of reactive oxygen species (ROS) or hydroperoxides. A significant increase of 12-lipoxygenase activities was observed in the presence of arachidonic acid (AA) under the GSH depletion. AA promoted the glutamate-induced cell death reducing caspase-3 activity and diminishing internucleosomal DNA fragmentation observed in apoptosis. Furthermore, AA diminished intracellular NAD, ATP and membrane potential revealing a dysfunction of mitochondrial membrane. Ac-DEVD, a caspase inhibitor, did not suppresse the glutamate-induced cytolysis. These results suggest that AA promotes cell death by inducing to necrosis from caspase-3 independent apoptosis through lipid peroxidation initiated by ROS or lipid hydroperoxides generated during the GSH depletion in C6 cells.Next, we studied the effect of AA on UV-induced cell death. At lethal dose, UV-C (254 nm) radiation induces cell dysfunction leading to apoptosis or necrosis. During the cell death of T-24 human bladder carcinoma cells, 1-2 Mbp giant DNA fragmentation was observed and consequently the DNA fragmentation was proceeded into high molecular weight 100-800 kbp DNA fragmentation followed by ladder-like inter-nucleosomal DNA fragmentation. Reactive lipid peroxides or oxygen species were not produced. In contrast, increase of caspase-3 and reduction of intracellular NAD and poly (ADP-ribose) polymerase were observed. UV-C radiation induces giant DNA fragmentation leading to apoptosis associated without producing DCFH detectable reactive oxygen species and with activation of caspase-3 and internucleosomal DNA fragmentation in T-24 carcinoma cells.
谷氨酸诱导的谷胱甘肽(GSH)耗竭通过活性氧(ROS)或氢过氧化物的积累导致C6大鼠胶质瘤细胞死亡。花生四烯酸(AA)的存在下,GSH耗竭的12-脂氧合酶的活性显着增加。AA促进谷氨酸诱导的细胞死亡,降低caspase-3活性,减少凋亡中观察到的核小体间DNA片段化。此外,AA还使细胞内NAD、ATP和膜电位降低,显示线粒体膜功能障碍。半胱天冬酶抑制剂Ac-DEVD不能抑制谷氨酸诱导的细胞溶解。这些结果表明,AA促进C6细胞死亡的机制可能是通过ROS或GSH耗竭过程中产生的脂质过氧化氢引发的脂质过氧化反应,诱导caspase-3非依赖性凋亡,进而导致细胞坏死。在致死剂量下,UV-C(254 nm)辐射诱导细胞功能障碍,导致细胞凋亡或坏死。在T-24人膀胱癌细胞死亡过程中,观察到1-2 Mbp的DNA大片段,随后DNA大片段变成高分子量的100-800 kbp的DNA片段,随后出现梯状的核小体间DNA片段。没有产生活性脂质过氧化物或氧物种。与此相反,caspase-3的增加和减少细胞内的NAD和聚(ADP-核糖)聚合酶观察。在T-24癌细胞中,UV-C辐射诱导巨大的DNA片段化,导致细胞凋亡,而不产生DCFH可检测到的活性氧,并激活caspase-3和核小体间DNA片段化。

项目成果

期刊论文数量(40)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
(Review) The role of endonucleases in chromosomal DNA fragmentation associated with apoptosis and necrosis.
(综述)核酸内切酶在与细胞凋亡和坏死相关的染色体 DNA 断裂中的作用。
  • DOI:
  • 发表时间:
    2006
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Fukuhara;H.;Masuda;M.;Yageta;M.;Fukami;T.;Kuramochi;M.;Maruyama;T.;Kitamura;T.;Murakami;Y.;Higuchi Y.
  • 通讯作者:
    Higuchi Y.
Induction of detoxication enzymes in mice by naturally occurring allyl nitrile
天然烯丙腈诱导小鼠解毒酶
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tanii H;Higashi T;Nishimura F;Higuchi Y;Saijoh K
  • 通讯作者:
    Saijoh K
The role of lipid peroxidation in chromosomal DNA frag-mentation associated with cell death induced by glutathione depletion.
脂质过氧化在与谷胱甘肽耗竭诱导的细胞死亡相关的染色体 DNA 断裂中的作用。
(Review) Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress.
(综述)氧化应激诱导的细胞凋亡和坏死中的染色体DNA断裂。
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Higuchi;Y.;Azuma T.;Higuchi Y.
  • 通讯作者:
    Higuchi Y.
Ultraviolet ray induces chromosomal giant DNA fragmentation followed by internucleosomal DNA fragmentation associated with apoptosis in rat glioma cells
紫外线诱导大鼠神经胶质瘤细胞中染色体巨型 DNA 断裂,随后发生与细胞凋亡相关的核小体间 DNA 断裂
  • DOI:
  • 发表时间:
    2003
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Higuchi Y;Mizukami Y;Yoshimoto T.
  • 通讯作者:
    Yoshimoto T.
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HIGUCHI Yoshihiro其他文献

HIGUCHI Yoshihiro的其他文献

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{{ truncateString('HIGUCHI Yoshihiro', 18)}}的其他基金

Targeted heart hyperthermia for heart failure using gold nano-rod
使用金纳米棒进行有针对性的心脏热疗治疗心力衰竭
  • 批准号:
    24591098
  • 财政年份:
    2012
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study on some proteins controling cell death in oxidative stress-induced neuronal cell death.
氧化应激诱导的神经细胞死亡中一些控制细胞死亡的蛋白质的研究。
  • 批准号:
    22590091
  • 财政年份:
    2010
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The relationship between the diagonal earlobe crease and the cardiovascular disease
耳垂斜纹与心血管疾病的关系
  • 批准号:
    21590900
  • 财政年份:
    2009
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Role of arachdonate cascade in apoptosis of neronal cells
花生四烯酸级联在神经元细胞凋亡中的作用
  • 批准号:
    10680580
  • 财政年份:
    1998
  • 资助金额:
    $ 1.92万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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  • 批准号:
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Role of TTYH1 in mobilizing lipids and ApoE in glia: Implications for brain aging and neurodegeneration
TTYH1 在神经胶质细胞动员脂质和 ApoE 中的作用:对大脑衰老和神经退行性变的影响
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Glia Exclusive Gene Therapy
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Elucidation of glia inflammation mechanisms common to degeneration and demyelination by novel pathogenic microglia
阐明新型致病性小胶质细胞退化和脱髓鞘常见的胶质炎症机制
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Molecular impact of endolysosomal dysfunction on neuron-glia communication pathways
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Reprogramming adult murine Müller glia via L-Myc expression
通过 L-Myc 表达对成年小鼠 Müller 胶质细胞进行重编程
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Role of neuron-satellite glia cell signaling in pelvic pain and visceral cross-sensitization
神经卫星胶质细胞信号传导在盆腔疼痛和内脏交叉敏化中的作用
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Enteric Glia is New Biological Target to Block Drug Resistance in Colon Cancer
肠胶质细胞是阻断结肠癌耐药性的新生物靶点
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Neuron-satellite glia interactions in the sympathetic nervous system
交感神经系统中神经元-卫星胶质细胞的相互作用
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Elucidating and bypassing molecular mechanisms that suppress Muller glia-dependent regeneration of cones in two zebrafish models of chronic retinal damage
阐明和绕过抑制两种慢性视网膜损伤斑马鱼模型中穆勒胶质细胞依赖性视锥细胞再生的分子机制
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