Low-Intensity Ultrasound Decreases α-Synuclein Aggregation via Attenuation of Mitochondrial Reactive Oxygen Species in MPP(+)-Treated PC12 Cells

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 alpha-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/cm(2). Furthermore, LIUS stimulation at 100 mW/cm(2) suppressed inhibition of mitochondrial complex activity byMPP(+) and actually resulted in a decrease of a-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 a-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 a-synuclein aggregation in PC12 cells.