title: Involvement of ERK1/2 pathway in neuroprotective effects of pyrroloquinoline quinine against rotenone-induced SH-SY5Y cell injury.
abstract: Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been shown to protect neurons against glutamate-induced damage both in vitro and in vivo. In this study, specific inhibitors to each of the mitochondrial complexes were used to find out which reactive oxygen species (ROS)-generating sites could be affected by PQQ. Then we established an in vitro model of Parkinson's disease (PD) by exposing cultured SH-SY5Y dopaminergic cells to rotenone, a complex I inhibitor. The neuroprotective effects of PQQ were observed by pretreatment of SH-SY5Y cells with PQQ before rotenone injury, and the possible involvement of certain signaling pathways were investigated. PQQ pretreatment prevented SH-SY5Y cells from rotenone-induced apoptosis in a concentration-dependent manner. PQQ neuroprotection was associated with inhibition of intracellular ROS production, modulation of the expression of apoptosis-related Bcl-2 and Bax, and regulation of the level of superoxide dismutase, glutathione, and malondialdehyde. Meanwhile, PQQ up-regulated the gene expression of Ndufs 1, 2, and 4 (complex I subunits), and increased mitochondrial viability and mitochondrial DNA content. Furthermore, PQQ pretreatment activated ERK1/2 phosphorylation in rotenone-injured SH-SY5Y cells, while ERK1/2 inhibition suppressed PQQ neuroprotection. All the results suggested that PQQ could protect SH-SY5Y cells against rotenone injury by reducing ROS production and maintaining mitochondrial functions through activation of ERK1/2 pathway.
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China; Co-innovation Center of Neuroregeneration, Nantong, JS 226001, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China; Department of Neurology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, JS 226001, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China; Department of Neurology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, JS 226001, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, JS 226001, PR China.
authors.forename: K
authors.initials: K
authors.lastname: Ke
authors.affiliation: Jiangsu Key Laboratory of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China; Co-innovation Center of Neuroregeneration, Nantong, JS 226001, PR China. Electronic address: dingfei@ntu.edu.cn.
authors.forename: F
authors.initials: F
authors.lastname: Ding
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000378:metabolism; D042967:Electron Transport Complex I; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009245:NADH Dehydrogenase / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D045542:PQQ Cofactor / Q000494:pharmacology*; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone; D013482:Superoxide Dismutase / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D004272:DNA, Mitochondrial; C487793:NDUFS1 protein, human; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D012402:Rotenone; D008315:Malondialdehyde; D045542:PQQ Cofactor; D013482:Superoxide Dismutase; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I; C496411:NDUFS2 protein, human; C427643:NDUFS4 protein, human; D005978:Glutathione
keywords: ERK1/2; neuroprotection; pyrroloquinoline quinine (PQQ); rotenone