Comparative proteomics study of mitochondrial electron transport system modulation in SH-SY5Y cells following MPP+ versus 6-OHDA-induced neurodegeneration

Parkinson's disease (PD) is the second-most common neurodegenerative disease worldwide. Several studies have investigated PD for decades; however, the exact mechanism of disease development remains unknown. To study PD, SH-SY5Y cells are often treated with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+) to induce PD. To understand the mechanism of PD pathogenesis, we confirmed protein changes between 6-OHDA- and MPP+-treated SH-SY5Y cells via proteomics analysis using liquid chromatography coupled with tandem mass spectrometry. 6-OHDA-treated SH-SY5Y cells showed increased expression of electron transporter-related proteins compared to that in the control group, along with decreased expression in MPP+-treated SH-SY5Y cells. However, both down- and upregulation of electron transporter-related proteins increased mitochondrial dysfunction and apoptosis. These proteins were confirmed via protein-protein interaction network analysis using IPA and STRING to induce mitochondrial dysfunction and apoptosis. Cell-based experiments using flow cytometry verified that apoptosis and mitochondrial membrane potential were increased in both 6-OHDA- and MPP+-treated SH-SY5Y cells. Our results provide new insights into PD pathogenesis, thereby contributing to the understanding of the mechanisms of PD development.