title: Pyrroloquinoline quinone against glutamate-induced neurotoxicity in cultured neural stem and progenitor cells.
abstract: Pyrroloquinoline quinone (PQQ), as a well-known redox enzyme cofactor, has been proven to play important roles in the regulation of cellular growth and development in mammals. Numerous physiological and medicinal functions of PQQ have so far been reported although its effect on neural stem and progenitor cells (NS/PCs) and the potential mechanism were even rarely investigated. In this study, the neuroprotective effects of PQQ were observed by pretreatment of NS/PCs with PQQ before glutamate injury, and the possible mechanisms were examined. PQQ stimulated cell proliferation and markedly attenuated glutamate-induced cell damage in a dose-dependent manner. By observing the nuclear morphological changes and flow cytometric analysis, PQQ pretreatment showed its significant effect on protecting NS/PCs against glutamate-induced apoptosis/necrosis. PQQ neuroprotection was associated with the decrease of intracellular reactive oxygen species (ROS) production, the increase of glutathione (GSH) levels, and the decrease of caspase-3 activity. In addition, pretreatment with PQQ also significantly enhanced the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) in the NS/PCs exposed to glutamate. These results suggest that PQQ can protect NS/PCs against glutamate toxicity associated with ROS-mediated mitochondrial pathway, indicating a useful chemical for the clinical application of NS/PCs.
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Dalian University of Technology, 116024 Dalian, China. Electronic address: guanshui@dlut.edu.cn.
authors.forename: Shui
authors.initials: S
authors.lastname: Guan
authors.affiliation: School of Life Science and Medicine, Dalian University of Technology, Panjin Campus, 124221 Panjin, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Dalian University of Technology, 116024 Dalian, China.
authors.forename: Yifu
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Dalian University of Technology, 116024 Dalian, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ge
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Dalian University of Technology, 116024 Dalian, China.
authors.forename: Tianqing
authors.initials: T
authors.lastname: Liu
authors.affiliation: Stem Cell and Tissue Engineering Laboratory, Dalian University of Technology, 116024 Dalian, China.
authors.forename: Xuehu
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Engineering Science, Oxford University, OX1 3PJ Oxford, UK.
authors.forename: Zhanfeng
authors.initials: Z
authors.lastname: Cui
mesh_terms: D000818:Animals; D017304:Annexin A5; D000873:Anthracenes; D017209:Apoptosis / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053145:Cell Nucleus Size / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018698:Glutamic Acid / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D009336:Necrosis / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D045542:PQQ Cofactor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D012844:Sincalide / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*
chemical_list: C546739:AnOV compound; D017304:Annexin A5; D000873:Anthracenes; D018690:Excitatory Amino Acid Agonists; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D045542:PQQ Cofactor; D005979:Glutathione Peroxidase; D053148:Caspase 3; D001973:Bromodeoxyuridine; D005978:Glutathione; D012844:Sincalide
keywords: Glutamate; Neural stem and progenitor cells; Neuroprotection; Pyrroloquinoline quinone; Reactive oxygen species