PQQ可逆转神经退化?大脑受损的老年人有福了
氧化应激的氧化还原感受器PQQ或作为帮助神经元生长的信号分子
【文献解读】
2015年2月中国大连理工大学的研究团队和英国牛津大学的研究团队共同在期刊《International Journal of Developmental Neuroscience》上发表了吡咯喹啉醌(PQQ)对谷氨酸诱导的细胞损伤的减缓作用。
本试验中,取孕13.5d的大鼠海马区胚胎神经组织标本,在无血清培养基中反复研磨分离细胞。用台盼蓝拒染法在血细胞计数仪上计数活细胞数。然后用CCK-8法测定细胞存活率;用荧光显微镜计数BrdU掺入的细胞数,计算BrdU/总细胞的比值;用Caspase-3/CPP32比色检测试剂盒测定caspase-3活性;最后用荧光微板仪和用ApoGSHTMGlutathione比色检测试剂盒测定细胞内总GSH水平。结果表明,PQQ处理后BrdU免疫反应细胞数显著增加。PQQ通过抑制caspase-3级联抑制谷氨酸诱导的NS/PC细胞凋亡。PQQ可显著增强对谷氨酸诱导的NS/PC细胞内ROS、总GSH水平及SOD、CAT和GPx活性的。
注:PQQ对NS/PC细胞增殖的影响
PQQ能够清除线粒体中的ROS并减轻氧化应激,从而对氧化应激诱导的心、肝和脑细胞损伤起到保护作用。PQQ最有前景的应用可能是神经保护,这可能暗示PQQ作为氧化应激的氧化还原感受器或作为帮助神经元生长的信号分子的功能。
【文献节选】
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.