Neuronal cell death mediated by mitochondria

线粒体介导的神经细胞死亡

• 批准号: 21659018
• 负责人: YONEDA Yukio
• 金额: $ 2.1万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21659018/
• 关键词: ミトコンドリア; 神経細胞死; NMDA; グルタミン酸; 脳虚血; NMDAレセプター; UCP2; 人口チャネル; Ca2+蛍光イメージング; NMDA受容体; ミトコンドリア膜電位; ミトコンドリア内カルシウム濃度; mPTP; 海馬神経細胞; 細胞内遊離カルシウム濃度

Glutamate neurotoxicity was found to at least in part involve mitochondrial membrane potential disruption, mPTP orchestration, mitochondrial free Ca^<2+> levels and UCP2 expression in rat hippocampal and cortical neurons. In HEK293 cells with acquired NMDAR channels and overexpressed UCP2, a more marked increase was seen in mitochondrial free Ca^<2+> levels, in addition to more severe cell death, after the exposure to NMDA than in cells without UCP2 overexpression. Accordingly, UCP2 could play a role as a determinant of the neurotoxicity mediated by NMDAR through a mechanism related to the modulation of mitochondrial free Ca^<2+> levels in neurons.

发现谷氨酸神经毒性至少部分涉及大鼠海马和皮质神经元中的线粒体膜电位破坏、mPTP协调、线粒体游离Ca 2+ 水平和UCP2表达。在具有获得性NMDAR通道和过表达UCP2的HEK293细胞中，与没有UCP2过表达的细胞相比，在暴露于NMDA之后除了更严重的细胞死亡之外，还观察到线粒体游离Ca 2+ 水平更显着的增加。因此，UCP2可以通过与神经元中线粒体游离Ca 2+ 水平的调节相关的机制发挥作为由NMDAR介导的神经毒性的决定因素的作用。

项目成果

Natural polyamines spermidine and spermine prevent bone loss through preferential disturbance of osteoclastic activation in ovariectomized mice

天然多胺亚精胺和精胺通过优先干扰卵巢切除小鼠的破骨细胞活化来防止骨质流失

• 发表时间: 2012
• 期刊: Br J Pharmacol
• 作者: Yamamoto T;Hinoi E;Fujita H;Iezaki T;Takahata Y;Takamori M & Yoneda Y
• 通讯作者: Takamori M & Yoneda Y

A pivotal role of mitochondrial free calcium in neurotoxicity mediated by pN-methyl-D-aspartate receptors in cultured rat hippocampal neurons.

线粒体游离钙在培养的大鼠海马神经元中 pN-甲基-D-天冬氨酸受体介导的神经毒性中发挥关键作用。

• 发表时间: 2011
• 期刊: Neurochem Int
• 影响因子: 4.2
• 作者: Yukari Nakamura;Eiichi Hinoi;Takeshi Takarada;Yoshifumi Takahata;Tomomi Yamamoto;Hiroyuki Fujita;Saya Takada;Syota Hashizume;Yukio Yoneda;Kambe Y
• 通讯作者: Kambe Y

Possible involvement of mitochondrial uncoupling protein-2 in cytotoxicity mediated by acquired N-methyl-D-aspartate receptor channels

• DOI: 10.1016/j.neuint.2012.03.019
• 发表时间: 2012-09-01
• 期刊: NEUROCHEMISTRY INTERNATIONAL
• 影响因子: 4.2
• 作者: Fukumori, Ryo;Takarada, Takeshi;Yoneda, Yukio
• 通讯作者: Yoneda, Yukio

Transactivation by runt related factor-2 of matrix metalloprotginase-13 in astrocytes.

星形胶质细胞中基质金属蛋白酶 13 的 runt 相关因子 2 的反式激活。

• 发表时间: 2009
• 期刊: Neurosci.Lett. 451
• 作者: Takarada T.;Yoneda Y.
• 通讯作者: Yoneda Y.

神經細胞新生促進租成物

促进细胞新生的化合物

• 发表时间: 2010