title: Rotenone directly induces BV2 cell activation via the p38 MAPK pathway.
abstract: Parkinson's disease (PD) is the second most common neurodegenerative disease. Although its pathogenesis is still unclear, increasing evidence suggests that mitochondrial dysfunction induced by environmental toxins, such as mitochondrial complex I inhibitors, plays a significant role in the disease process. The microglia in PD brains are highly activated, and inflammation is also an essential element in PD pathogenesis. However, the means by which these toxins activate microglia is still unclear. In the present study, we found that rotenone, a mitochondrial complex I inhibitor, could directly activate microglia via the nuclear factor kappa B (NF-κB) signaling pathway, thereby inducing significantly increased expression of inflammatory cytokines. We further observed that rotenone induced caspase-1 activation and mature IL-1β release, both of which are strictly dependent on p38 mitogen-activated protein kinase (MAPK). The activation of p38 is associated with the presence of reactive oxygen species (ROS) produced by rotenone. Removal of these ROS abrogated the activation of the microglia. Therefore, our data suggest that the environmental toxin rotenone can directly activate microglia through the p38 MAPK pathway.
authors: Laboratory of Molecular Neuropathology, Key Laboratory of Brain Function and Diseases and School of Life Sciences, University of Science & Technology of China, Chinese Academy of Sciences, Hefei, China.
authors: Feng
authors: F
authors: Gao
authors: Dong
authors: D
authors: Chen
authors: Qingsong
authors: Q
authors: Hu
authors: Guanghui
authors: G
authors: Wang
mesh_terms: D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology / Q000633:toxicity*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D058847:Inflammasomes / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D020935:MAP Kinase Signaling System; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000276:immunology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology / Q000633:toxicity*; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D004785:Environmental Pollutants; D058847:Inflammasomes; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D012402:Rotenone; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases
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