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A Proteomic Analysis of MCLR-induced Neurotoxicity: Implications for Alzheimer's Disease

文献类型： 外文期刊

作者： Li, Guangyu 1 ; Cai, Fei 2 ; Yan, Wei 3 ; Li, Cairong 2 ; Wang, Jianghua 1 ;

作者机构： 1.Huazhong Agr Univ, Coll Fisheries, Wuhan 430070, Peoples R China

2.Xianning Univ, Dept Pharmacol, Coll Med, Xianning 437100, Peoples R China

3.Hubei Acad Agr Sci, Inst Agr Qual Stand & Testing Technol, Wuhan 430064, Peoples R China

关键词： microcystin-LR;proteomic analysis;tau hyperphosphorylation;Alzheimer's disease

期刊名称：TOXICOLOGICAL SCIENCES （ 影响因子：4.849； 五年影响因子：4.996 ）

ISSN： 1096-6080

年卷期： 2012 年 127 卷 2 期

页码：

收录情况： SCI

摘要： Cyanobacteria-derived microcystin-leucine-arginine (MCLR), commonly characterized as a hepatotoxin, has recently been found to show neurotoxicity, but the exact mechanism is still unknown. To further our understanding of the neurotoxic effects of MCLR and the mechanisms behind it, we used two-dimensional gel electrophoresis and mass spectrometry analysis to identify global protein profiles associated with MCLR-induced neurotoxicity. MCLR-treated hippocampi showed alterations in proteins involved in cytoskeleton, neurodegenerative disease, oxidative stress, apoptosis, and energy metabolism. After validation by Western blot and quantitative real-time PCR, the expressions of three proteins related to neurodegenerative disease, septin 5, alpha-internexin, and alpha-synuclein, were identified to be altered by MCLR exposure. Based on our proteomic analysis that MCLR toxicity might be linked to neurodegeneration, we examined the activity of serine/threonine-specific protein phosphatases (PPs), which are markers of neurodegenerative disease. MCLR was found to induce inhibition of PPs and abnormal hyperphosphorylation of the neuronal microtubule-associated protein tau. This was found to lead to impairment of learning and memory, accompanied by severe histological damage and neuronal apoptosis in the hippocampal CA1 regions of rats. Our results support the hypothesis that MCLR could induce neurotoxic effects, the reason for which could be attributed to the disruption of the cytoskeleton, oxidative stress, and inhibition of PPs in the hippocampus. Moreover, MCLR was found to induce tau hyperphosphorylation, spatial memory impairment, neuronal degenerative changes, and apoptosis, suggesting that this cyanotoxin may contribute to Alzheimer's disease in humans.

  • 相关文献

[1]Global effects of subchronic treatment of microcystin-LR on rat splenetic protein levels. Li, Guangyu,Qiao, Qin,He, Yan,Zhang, Xuezhen,Yan, Wei,Chen, Jun,Cai, Fei. 2012

[2]Spatial Learning and Memory Impairment and Pathological Change in Rats Induced by Acute Exposure to Microcystin-LR. Li, Guangyu,Chen, Nan,Wang, Jianghua,Yan, Wei,Cai, Fei,Li, Cairong.

[3]Microcystin-LR inhibited hippocampal long-term potential via regulation of the glycogen synthase kinase-3 beta pathway. Wang, Jianghua,Zhou, Qiong,Lin, Fankai,Cai, Fei,Yan, Wei,Xie, Liqiang. 2013

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