Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production
- Department of Pathophysiology, Medical College, Qingdao University, Qingdao, Shandong 266071 (China)
- Department of Clinical Laboratory, the Affiliated Hospital of Medical College Qingdao University, 266003 Qingdao (China)
- Department of Pharmacology, Medical College, Qingdao University, Qingdao 266071 (China)
Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN{sub 3} to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-kB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation. - Highlights: • ETC inhibitors induce mitochondrial ROS production in microglia. • ETC inhibitors stimulated secretion of pro-inflammatory cytokines by micriglia. • MAPK/NF-κB pathways maybe related to the microglial activation by ETC inhibitors.
- OSTI ID:
- 22746405
- Journal Information:
- Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 340; ISSN 0014-4827; ISSN ECREAL
- Country of Publication:
- United States
- Language:
- English
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ADENINES
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