Mitochondrial dysfunction and oxidative stress promote apoptotic cell death in the striatum via cytochrome c/caspase-3 signaling cascade following chronic rotenone intoxication in rats.
Mitochondrial dysfunction and oxidative stress promote apoptotic cell death in the striatum via cytochrome c/caspase-3 signaling cascade following chronic rotenone intoxication in rats.
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DOI：
10.3390/ijms13078722
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发表时间：
2012
影响因子：
5.6
通讯作者：
Chuang YC
中科院分区：
文献类型：
--
作者：
Lin TK;Cheng CH;Chen SD;Liou CW;Huang CR;Chuang YC
帕金森病（PD）是一种以黑质纹状体多巴胺能变性为特征的进行性神经系统疾病。有证据表明，线粒体功能障碍可能通过多种不同的途径与PD相关，包括自由基产生和线粒体复合物I活性功能障碍。在刘易斯大鼠中，长期全身给予特定的线粒体复合物I抑制剂鱼藤酮（3 mg/kg/天）可产生帕金森样症状。鱼藤酮输注2-4周后，观察到纹状体中氧化蛋白和过氧亚硝酸盐的增加，以及Bim，Bax或细胞色素c的线粒体或细胞质易位。全身性鱼藤酮暴露28天后，酪氨酸羟化酶的免疫组化染色表明黑质纹状体多巴胺能神经元细胞变性。特征性的组织化学（TUNEL或活化的caspase-3染色）或超微结构（电子显微镜）特征的凋亡细胞死亡存在于慢性鱼藤酮中毒后的纹状体神经元细胞。我们的结论是，慢性鱼藤酮中毒可能会增强氧化和亚硝化应激，诱导线粒体功能障碍和超微结构损伤，导致易位的Bim和Bax从细胞质线粒体，有助于通过细胞色素c/caspase-3信号级联纹状体细胞凋亡。
Parkinson’s disease (PD) is a progressive neurological disorder marked by nigrostriatal dopaminergic degeneration. Evidence suggests that mitochondrial dysfunction may be linked to PD through a variety of different pathways, including free-radical generation and dysfunction of the mitochondrial Complex I activity. In Lewis rats, chronic systemic administration of a specific mitochondrial Complex I inhibitor, rotenone (3 mg/kg/day) produced parkinsonism-like symptoms. Increased oxidized proteins and peroxynitrite, and mitochondrial or cytosol translocation of Bim, Bax or cytochrome c in the striatum was observed after 2–4 weeks of rotenone infusion. After 28 days of systemic rotenone exposure, imunohistochemical staining for tyrosine hydroxylase indicated nigrostriatal dopaminergic neuronal cell degeneration. Characteristic histochemical (TUNEL or activated caspase-3 staining) or ultrastructural (electron microscopy) features of apoptotic cell death were present in the striatal neuronal cell after chronic rotenone intoxication. We conclude that chronic rotenone intoxication may enhance oxidative and nitrosative stress that induces mitochondrial dysfunction and ultrastructural damage, resulting in translocation of Bim and Bax from cytosol to mitochondria that contributes to apoptotic cell death in the striatum via cytochrome c/caspase-3 signaling cascade.
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DOI：
10.1042/bj20111451
发表时间：
2012-01-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Lee J;Giordano S;Zhang J
通讯作者：
Zhang J
影响因子：
10.6
作者：
Carreras, Maria C.;Franco, Maria C.;Poderoso, Juan J.
通讯作者：
Poderoso, Juan J.
影响因子：
3.8
作者：
Horowitz, JM;Pastor, DM;Torres, G
通讯作者：
Torres, G
影响因子：
7.4
作者：
Cadenas, E;Davies, KJA
通讯作者：
Davies, KJA
影响因子：
3
作者：
Chuang, Yao-Chung;Lin, Jui-Wei;Chang, Wen-Neng
通讯作者：
Chang, Wen-Neng