Mitochondrial superoxide dismutase SOD2, but not cytosolic SOD1, plays a critical role in protection against glutamate-induced oxidative stress and cell death in HT22 neuronal cells.
Mitochondrial superoxide dismutase SOD2, but not cytosolic SOD1, plays a critical role in protection against glutamate-induced oxidative stress and cell death in HT22 neuronal cells.
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DOI：
10.1016/j.freeradbiomed.2009.12.024
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发表时间：
2010-03-15
影响因子：
7.4
通讯作者：
Zhu, Bao Ting
中科院分区：
文献类型：
--
作者：
Fukui, Masayuki;Zhu, Bao Ting
氧化性细胞死亡是神经退行性疾病的重要促成因素。使用HT22小鼠海马神经元细胞作为模型，我们试图证明线粒体是谷氨酸诱导的氧化性细胞死亡的关键早期目标。我们发现，当HT22细胞转染shRNA敲低线粒体超氧化物歧化酶（SOD 2），这些细胞变得更容易受到谷氨酸诱导的氧化性细胞死亡。在谷氨酸暴露后的早期时间点，易感性的增加伴随着线粒体超氧化物的积累增加和正常线粒体形态和功能的丧失。然而，SOD 2在这些细胞中的过表达降低线粒体超氧化物水平，保护其形态和功能，并提供对谷氨酸诱导的氧化细胞毒性的抗性。这些SOD2改变的HT22细胞的敏感性的变化是神经毒素特异性的，因为过氧化氢的细胞毒性在这些细胞中没有改变。此外，选择性敲除培养的HT 22细胞中的胞质SOD 1并没有明显改变其对谷氨酸或过氧化氢的敏感性。这些发现表明，线粒体SOD 2在保护神经细胞免受谷氨酸诱导的氧化应激和细胞毒性中起着关键作用。这些数据还表明，线粒体是谷氨酸诱导的氧化神经毒性的重要早期靶点。
Oxidative cell death is an important contributing factor in neurodegenerative diseases. Using HT22 mouse hippocampal neuronal cells as a model, we sought to demonstrate that mitochondria are crucial early targets of glutamate-induced oxidative cell death. We showed that when HT22 cells were transfected with shRNA for knockdown of the mitochondrial superoxide dismutase (SOD2), these cells became more susceptible to glutamate-induced oxidative cell death. The increased susceptibility was accompanied by increased accumulation of mitochondrial superoxide and loss of normal mitochondrial morphology and functions at early time points following glutamate exposure. However, overexpression of SOD2 in these cells reduced mitochondrial superoxide level, protected its morphology and functions, and provided resistance against glutamate-induced oxidative cytotoxicity. The change in the sensitivity of these SOD2-altered HT22 cells was neurotoxicant-specific, because the cytotoxicity of hydrogen peroxide was not altered in these cells. In addition, selective knockdown of the cytosolic SOD1 in cultured HT22 cells did not appreciably alter their susceptibility to either glutamate or hydrogen peroxide. These findings show that the mitochondrial SOD2 plays a critical role in protecting neuronal cells from glutamate-induced oxidative stress and cytotoxicity. These data also indicate that mitochodria are important early targets of glutamate-induced oxidative neurotoxicity.
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DOI：
10.1002/neu.480230915
发表时间：
1992-11-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
CHOI, DW
通讯作者：
CHOI, DW
影响因子：
16.2
作者：
MURPHY, TH;MIYAMOTO, M;COYLE, JT
通讯作者：
COYLE, JT
影响因子：
4.8
作者：
Connor, KM;Subbaram, S;Melendez, JA
通讯作者：
Melendez, JA
影响因子：
7.4
作者：
Jung, T;Engels, M;Grune, T
通讯作者：
Grune, T
DOI：
10.1073/pnas.96.3.846
发表时间：
1999-02-02
影响因子：
11.1
作者：
Melov, S;Coskun, P;Wallace, DC
通讯作者：
Wallace, DC