Wang Di, Hu Shuang, Zhang Junrong, Li Qiuyue, Liu Xinyu, Li Yu
Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, Jilin 130118, P.R. China.
School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
Mol Med Rep. 2017 Aug;16(2):1133-1138. doi: 10.3892/mmr.2017.6745. Epub 2017 Jun 9.
The present study aimed to investigate the neuroprotective effect of a novel synthetic compound (5zou) on differentiated PC12 cells against 6‑hydroxydopamine (6‑OHDA) and L‑glutamic acid (L‑Glu) neurotoxin‑induced cell injury and the potential mechanisms involved. 5zou is a 2, 2‑disubstituted 1,2‑dihydropyridine. PC12 cells were treated with 6‑OHDA and L‑Glu to establish neurotoxic cell models. MTT assay, DCFH‑DA staining, Fluo‑4‑AM staining, JC‑1 staining and western blotting were used to determine the changes in cell viability, intracellular reactive oxygen species concentration, Ca2+ influx, mitochondrial membrane potential and the protein expressions of B‑cell lymphoma‑2 (Bcl‑2) and B‑cell lymphoma‑extra large (Bcl‑xL). Morphological analysis demonstrated the effect of 5zous on neuritogenesis and differentiation in PC12 cells. The results suggested that 5zou rescued the cell viability, intracellular ROS level, Ca2+ influx, mitochondrial membrane potential, and expression of Bcl‑2 and Bcl‑xL, which were altered by 6‑OHDA and L‑Glu. The study confirmed that 5zou has neuroprotective effects on neurotoxin‑induced differentiated PC12 cells injury, potentially via the mitochondrial apoptosis pathway.
本研究旨在探讨一种新型合成化合物(5zou)对分化的PC12细胞免受6-羟基多巴胺(6-OHDA)和L-谷氨酸(L-Glu)神经毒素诱导的细胞损伤的神经保护作用及其潜在机制。5zou是一种2,2-二取代的1,2-二氢吡啶。用6-OHDA和L-Glu处理PC12细胞以建立神经毒性细胞模型。采用MTT法、DCFH-DA染色、Fluo-4-AM染色、JC-1染色和蛋白质印迹法来测定细胞活力、细胞内活性氧浓度、Ca2+内流、线粒体膜电位以及B细胞淋巴瘤-2(Bcl-2)和B细胞淋巴瘤-超大(Bcl-xL)的蛋白质表达变化。形态学分析证明了5zou对PC12细胞神经突发生和分化的影响。结果表明,5zou挽救了被6-OHDA和L-Glu改变的细胞活力、细胞内ROS水平、Ca2+内流、线粒体膜电位以及Bcl-2和Bcl-xL的表达。该研究证实5zou对神经毒素诱导的分化PC12细胞损伤具有神经保护作用,其潜在机制可能是通过线粒体凋亡途径。