Peroxiredoxin 5 (Prx5) decreases LPS-induced microglial activation through regulation of Ca2+/calcineurin-Drp1-dependent mitochondrial fission = 페록시레독신 5 (Prx5)가Ca2+/calcineurin-Drp1-dependent mitochondrial fission을 통하여 LPS로 유발된 마이크로글리아 세포 활성화를 억제하는 기전
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- Peroxiredoxin 5 (Prx5) decreases LPS-induced microglial activation through regulation of Ca2+/calcineurin-Drp1-dependent mitochondrial fission = 페록시레독신 5 (Prx5)가Ca2+/calcineurin-Drp1-dependent mitochondrial fission을 통하여 LPS로 유발된 마이크로글리아 세포 활성화를 억제하는 기전
- J Park; H Choi; B Kim; U Chae; D G Lee; Sang-Rae Lee; S Lee; H S Lee; D S Lee
- Bibliographic Citation
- Free Radical Biology and Medicine, vol. 99, pp. 392-404
- Publication Year
- 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.
- Calcineurin; Microglia; Mitochondrial dynamics; Peroxiredoxin; ROS
- Appears in Collections:
- Ochang Branch Institute > Division of Bioinfrastructure > National Primate Research Center > 1. Journal Articles
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