Parkin in early stage LPS-stimulated BV-2 cells regulates pro-inflammatory response and mitochondrial quality via mitophagy

• Published in: Journal of neuroimmunology 2019-11, Vol.336, p.577044-577044, Article 577044
• Main Authors: Yun, Hye Keun, Park, Junghyung, Chae, UnBin, Lee, Hyun-Shik, Huh, Jae-Won, Lee, Sang-Rae, Bae, Yong Chul, Lee, Dong-Seok
• Format: Article
• Language: English
• Subjects: Lipopolysaccharide; Microglia; Mitochondrial quality control; Mitophagy; Neuro-inflammation; Parkin
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/j.jneuroim.2019.577044

Numerous literature related to the role of Parkin and mitophagy focuses on neurons, but not microglial cells, responsible for most inflammatory responses in the central nervous system. Here, we first observed that Parkin expression in BV-2 microglial cells increased up to 6 hours (early stage) after LPS stimulation and decreased after that. Overexpression Parkin substantially suppressed the pro-inflammatory response and control of pro-inflammatory mediators is through regulation of MAPK and NF-κB signal in BV-2 cells. Therefore, these results demonstrate that early LPS-induced Parkin controls the inflammatory response by modulating MAPK and retains mitochondrial quality through mitophagy in microglial cells. Early induced Parkinafter LPS stimulation mediates mitophagyfor mitochondrial quality and regulation of pro-inflammatory response in BV-2 microglial cells. LPS, Lipopolysaccharide; mtROS, mitochondrial Reactive Oxygen Species; Δψ, mitochondrial membrane potential; Ub, Ubiquitin; MAPK, Mitogen-activated protein kinase. Red arrows imply stressful situation by LPS stimulation, skybluearrows indicate down-regulation of stressful factors by Parkinexpression, and lightgreyarrows means general pathway induced by LPS stimulation. [Display omitted] •Parkin accrued up to 6 hr and decreased after that in BV-2 microglial cells with LPS stimulation.•Parkin suppresses production of pro-inflammatory mediators by LPS.•Parkin down-regulates elevated levels of intracellular/mitochondrial ROS in activated microglial cells.•Parkin rescues decreased mitochondrial membrane potential.•Parkin suppresses LPS-induced MAPKs and NF-κB activation.