期刊
BRAIN RESEARCH
卷 1622, 期 -, 页码 43-50出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2015.06.008
关键词
Parkinson's disease; Rifampicin; Rotenone; Oxidative stress; Microglia
资金
- National Natural Science Foundation of China [81371391]
- Medical Scientific Research Foundation of Guangdong Province, China [B2014130]
- Natural Science Foundation of Guangdong Province [2014A030313202]
- National Innovative Entrepreneurial Training Program of College Students [201410558098]
- Key Laboratory of Malignant Tumor Molecular Mechanism and Translational Medicine of Guangzhou Bureau of Science and Information Technology [[2013] 163]
- Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes [KLB09001]
A growing body of evidence has supported that environmental factors, such as exposure to heavy metal and pesticides, play an important role in the pathogenesis of Parkinson's disease (PD). Rotenone, the active ingredient in various pesticides, has been identified as an inducer of PD. It has been revealed that rotenone induces activation of microglia and generation of pro-inflammatory factors in PD. Our previous studies demonstrated that rifampicin possessed neural protective effect in PD. In this study, we aimed to study the effect of rifampicin on the inflammation induced by rotenone in microglia and the underlying mechanisms. Results demonstrated that rifampicin pretreatment significantly reduced rotenone-induced cytotoxicity and gene expression of IL-1 beta in BV2 microglia. Moreover, western blot analysis verified that rifampicin pretreatment suppressed NLRP3 inflammasome activation via inhibiting caspase-1 cleavage and protein expression of NLRP3. As it is indicated that reactive oxidative stress (ROS) is one of the activators for NLRP3 inflammasome, we further employed 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) staining and Fthodamine123 staining to detect intracellular ROS and mitochondrial membrane potential (MMP), respectively. Results confirmed that rifampicin obviously reduced intracellular ROS and reversed loss of MMP in BV2 cells treated by rotenone. Taken together, our data indicate that rifampicin pretreatment inhibits maturation of IL-1 beta and neuroinflammation induced by rotenone via attenuating NLRP3 inflammasome activation. Rifampicin might emerge as a promising candidate for modulating neuroinflammation in PD. (C) 2015 Elsevier B.V. All rights reserved.
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