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Neurosci Lett. 2018 Nov 20;687:104-110. doi: 10.1016/j.neulet.2018.09.031. Epub 2018 Sep 18.

Mitochondrial regulation by pyrroloquinoline quinone prevents rotenone-induced neurotoxicity in Parkinson's disease models.

Author information

1
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
2
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China; Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 20 Xisi Road, Nantong, JS 226001, PR China.
3
Medical School of Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China.
4
Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong, JS 226001, PR China; Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 20 Xisi Road, Nantong, JS 226001, PR China. Electronic address: zhangqi@ntu.edu.cn.

Abstract

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 mitochondrial mechanisms involved in the neuroprotection of PQQ both in vitro and in vivo. The cultured human SH-SY5Y neuroblastoma cells were exposed to different concentrations of PQQ after which the cells were treated with rotenone. Electron microscopy images showed that PQQ could prevent the mitochondrial morphology damage. The down-regulation of mitochondrial biogenesis related genes (PGC-1alpha and TFAM) and mitochondrial fission and fusion related genes (Drp1and Mfn2) in rotenone-injured SH-SY5Y cells could be inhibited by PQQ. PQQ could also promote the transposition of Drp1 and Mfn2 from cytosol to mitochondria. In addition, rotenone was injected into the left medial forebrain bundle of SD rats to establish a Parkinson's disease (PD) model in vivo, after which different doses of PQQ or Edaravone were given intraperitoneally once daily for 8 weeks. PQQ could up-regulate the mRNA levels of PGC-1alpha, TFAM, Drp-1 and Mfn2 in the midbrain of PD rats. Our findings indicated that PQQ could prevent mitochondrial dysfunction by promoting mitochondrial biogenesis and regulating mitochondrial fission and fusion, which might contribute to its neuroprotective effect in PD models.

KEYWORDS:

Mitochondria; Neuroprotection; Parkinson’s disease; Pyrroloquinoline quinone; Rotenone

PMID:
30240821
DOI:
10.1016/j.neulet.2018.09.031
[Indexed for MEDLINE]

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