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Rotenone Could Activate Microglia Through NFκB Associated Pathway

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Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease, and its etiology remains obscure. Increasing evidence has suggested an important role for environmental factors such as exposure to pesticides in increasing the risk of developing PD and inflammation is the early incident during the process of PD. In this study, we measure the pro-inflammatory cytokines by enzyme-linked immunosorbnent assay and RT-PCR methods; analyze the reactive oxygen species by DCFH-DA; detected nuclear factor κB (NFκB) translocation by western blot and immunofluorescence methods; and analyze the phosphorylation of mitogen-activated protein (MAP) kinase and protein level of Nurr1 by western blot. Results showed that rotenone could induce tumor neurosis factor α (TNFα) and interleukin 1β (IL-1β) release from BV-2 cells, enhance TNFα and IL-1β mRNA levels in substantia nigra lesioned by rotenone; also, rotenone could increase the phosphorylation of inhibitor of κB (IκB), extracellular regulated protein kinase , c-Jun N-terminal kinase, p38 MAP kinases and promote p65 subunit of NFκB translocation to nuclear; at the same time, rotenone could decrease the protein level of Nurr1 in nuclear. So, rotenone exerted toxicity through activating microglia, and its mechanism might be associated with NFκB signal pathway.

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Acknowledgments

This work was supported by National Natural Science Foundation of China Grants (No. 81274122, 81102831, 81073078), Special Purpose for New Drug Development (2012ZX09301002-004), Studies on Structure and function of Bioactive Substances from Natural Medicines (IRT1007), National Natural Science Foundation of Beijing Grants (7131013), Research Fund for the Doctoral Program of Higher Education of China (20121106130001).

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Authors and Affiliations

  1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Xiannongtan Street, Xuanwu District, Beijing, 100050, People’s Republic of China

    Yu-he Yuan, Jian-dong Sun, Miao-miao Wu, Jin-feng Hu, Shan-ying Peng & Nai-Hong Chen

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  1. Yu-he Yuan
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  2. Jian-dong Sun
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  3. Miao-miao Wu
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  4. Jin-feng Hu
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  6. Nai-Hong Chen
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Correspondence to Nai-Hong Chen.

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Yuan, Yh., Sun, Jd., Wu, Mm. et al. Rotenone Could Activate Microglia Through NFκB Associated Pathway. Neurochem Res 38, 1553–1560 (2013). https://doi.org/10.1007/s11064-013-1055-7

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