title: Low-Intensity Ultrasound Decreases α-Synuclein Aggregation via Attenuation of Mitochondrial Reactive Oxygen Species in MPP(+)-Treated PC12 Cells.
abstract: Many studies have shown that mitochondrial dysfunction and the subsequent oxidative stress caused by excessive reactive oxygen species (ROS) generation play a central role in the pathogenesis of Parkinson's disease (PD). We have previously shown that low-intensity ultrasound (LIUS) could reduce ROS generation by L-buthionine-(S,R)-sulfoximine (BSO) in retinal pigment epithelial cells. In this study, we studied the effects of LIUS stimulation on the ROS-dependent α-synuclein aggregation in 1-methyl-4-phenylpyridinium ion (MPP+)-treated PC12 cells. We found that LIUS stimulation suppressed the MPP+-induced ROS generation and inhibition of mitochondrial complex I activity in PC12 cells in an intensity-dependent manner at 30, 50, and 100 mW/cm2. Furthermore, LIUS stimulation at 100 mW/cm2suppressed inhibition of mitochondrial complex activity by MPP+and actually resulted in a decrease of α-synuclein phosphorylation and aggregation induced by MMP+treatment in PC12 cells. LIUS stimulation also inhibited expression of casein kinase 2 (CK2) that appears to mediate ROS-dependent α-synuclein aggregation. Finally, LIUS stimulation alleviated the death of PC12 cells by MPP+treatment in an intensity-dependent manner. We, hence, suggest that LIUS stimulation inhibits ROS generation by MPP+treatment, thereby suppressing α-synuclein aggregation in PC12 cells.
authors.affiliation: Department of Physiology, Inha University College of Medicine, Incheon, 22212, South Korea.
authors.forename: Mrigendra Bir
authors.initials: MB
authors.lastname: Karmacharya
authors.affiliation: Department of Biomedical Sciences, Inha University College of Medicine, Incheon, 22212, South Korea.
authors.forename: Binika
authors.initials: B
authors.lastname: Hada
authors.affiliation: Department of Physiology, Inha University College of Medicine, Incheon, 22212, South Korea. srpark@inha.ac.kr.
authors.forename: So Ra
authors.initials: SR
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, Inha University College of Medicine, Incheon, 22212, South Korea. bryan@inha.ac.kr.
authors.forename: Byung Hyune
authors.initials: BH
authors.lastname: Choi
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000069453:Ultrasonic Waves; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D051844:alpha-Synuclein; D015655:1-Methyl-4-phenylpyridinium
keywords: 1-Methyl-4-phenylpyridinium ion (MPP+); Low-intensity ultrasound (LIUS); Mitochondrial dysfunction; Parkinson’s disease (PD); Reactive oxygen species (ROS); α-Synuclein