Neuroprotective effects of pyrroloquinoline quinone against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson's disease.
Mitochondrial dysfunction and oxidative stress have been implicated in the pathogenesis of Parkinson's disease (PD). Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has been reported to protect SH-SY5Y cells from cytotoxicity induced by rotenone, a mitochondrial complex I inhibitor. In this study, we aimed to investigate the neuroprotective effects of PQQ against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson's disease. Pre-treatment with PQQ prevented cultured midbrain neurons from rotenone-induced apoptosis, restored mitochondrial membrane potential, inhibited intracellular reactive oxygen species (ROS) production, and affected microtubule depolymerization. On the other hand, intraperitoneal administration of PQQ exerted protective effects on rats that had received rotenone injection into the medial forebrain bundle through decreasing the apomorphine-evoked rotation, inhibiting neuronal loss and TH down-regulation in SNc, increasing the antioxidative ability, and regulating intracellular expressions of Ndufs1 and Ndufs 4. Silencing of Ndufs1 or Ndufs4 in cultured SH-SY5Y cells or midbrain neurons reduced the neuroprotective effects of PQQ. Overall, our results suggest that PQQ neuroprotection may be mediated by the inhibition of mitochondrial dysfunction and oxidative stress as well as by the gene modulation of Ndufs1 and Ndufs4.
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Qi
Q
Zhang
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Shuhua
S
Chen
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Shu
S
Yu
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Jiaojiao
J
Qin
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Jingjing
J
Zhang
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
Qiong
Q
Cheng
Department of Neurology, Affiliated Hospital of Nantong University, 20 Xisi Road, Nantong, JS 226001, PR China.
Kaifu
K
Ke
Jiangsu Key Laboratory of Neuroregeneration, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China. Electronic address: dingfei@ntu.edu.cn.
Fei
F
Ding
D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008636:Mesencephalon / Q000187:drug effects* / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045542:PQQ Cofactor / Q000494:pharmacology / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000633:toxicity*; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D012402:Rotenone; D045542:PQQ Cofactor
Mitochondrial function; Neuroprotection; Parkinson's disease (PD); Pyrroloquinoline quinone (PQQ); Reactive oxygen species (ROS); Rotenone