title: Peroxiredoxin 5 (Prx5) decreases LPS-induced microglial activation through regulation of Ca2+/calcineurin-Drp1-dependent mitochondrial fission.
abstract: Microglial activation is a hallmark of neurodegenerative diseases. ROS activates microglia by regulating transcription factors to express pro-inflammatory genes and is associated with disruption of Ca2+homeostasis through thiol redox modulation. Recently, we reported that Prx5 can regulate activation of microglia cells by governing ROS. In addition, LPS leads to excessive mitochondrial fission, and regulation of mitochondrial dynamics involved in a pro-inflammatory response is important for the maintenance of microglial activation. However, the precise relationship among these signals and the role of Prx5 in mitochondrial dynamics and microglial activation is still unknown. In this study, we demonstrated that Ca2+/calcineurin-dependent de-phosphorylation of Drp1 induces mitochondrial fission and regulates mitochondrial ROS production, which influences the expression of pro-inflammatory mediators in LPS-induced microglia cells. Moreover, it is likely that cytosolic and Nox-derived ROS were upstream of mitochondrial fission and mitochondrial ROS generation in activated microglia cells. Prx5 regulates LPS-induced mitochondrial fission through modulation of Ca2+/calcineurin-dependent Drp1 de-phosphorylation by eliminating Nox-derived and cytosolic ROS. Therefore, we suggest that mitochondrial dynamics may be essential for understanding pro-inflammatory responses and that Prx5 may be used as a new therapeutic target to prevent neuroinflammation and neurodegenerative diseases.
authors: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors: Junghyung
authors: J
authors: Park
authors: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Jeollabuk-do, Republic of Korea.
authors: Hoonsung
authors: H
authors: Choi
authors: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors: Bokyung
authors: B
authors: Kim
authors: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors: Unbin
authors: U
authors: Chae
authors: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors: Dong Gil
authors: DG
authors: Lee
authors: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Chungcheongbuk-do, Republic of Korea.
authors: Sang-Rae
authors: SR
authors: Lee
authors: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Jeollabuk-do, Republic of Korea.
authors: Seunghoon
authors: S
authors: Lee
authors: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea.
authors: Hyun-Shik
authors: HS
authors: Lee
authors: School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea; College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea. Electronic address: lee1@knu.ac.kr.
authors: Dong-Seok
authors: DS
authors: Lee
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002461:Cell Line, Transformed; D034281:Dynamins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects* / Q000235:genetics; D000074624:NADPH Oxidase 1 / Q000235:genetics / Q000378:metabolism; D000074662:NADPH Oxidase 2 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D054464:Peroxiredoxins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D054464:Peroxiredoxins; C515975:Prdx5 protein, mouse; C488842:Cybb protein, mouse; D000074624:NADPH Oxidase 1; D000074662:NADPH Oxidase 2; C000614711:NOX1 protein, mouse; D019703:Calcineurin; C486391:Dnm1l protein, mouse; D034281:Dynamins; D002118:Calcium
keywords: Calcineurin; Microglia; Mitochondrial dynamics; Peroxiredoxin; ROS