白藜芦醇通过PI3K/Akt途径抵抗6-羟基多巴胺诱导的PC12细胞损伤。
Resveratrol against 6-OHDA-induced damage of PC12 cells via PI3K/Akt.
作者信息
Huang Nanqu, Huang Juan, Zhang Ying, Chen Mingji, Shi Jingshan, Jin Feng
机构信息
Drug Clinical Trial Institution, The Third Affiliated Hospital of Zunyi Medical University (The First People's Hospital of Zunyi), No. 98, Fenghuang Road, Zunyi 563000, Guizhou, China.
Department of Pharmacology and Chemical Biology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, No. 280, South Chongqing Road, Shanghai 200025, China.
出版信息
Transl Neurosci. 2021 Apr 19;12(1):138-144. doi: 10.1515/tnsci-2020-0165. eCollection 2021 Jan 1.
OBJECTIVE
Our previous study found that resveratrol (Res), which is a phytoalexin, attenuated 6-hydroxydopamine (6-OHDA)-induced motor dysfunction by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in rats. Therefore, we further explored the protective effect of Res on 6-OHDA-induced damage to PC12 cells with respect to the PI3K/Akt signaling pathway.
METHODS
We incubated PC12 cells with 75 μM 6-OHDA for 24 h, and Res was then added at a final concentration of 25 μM; the protective effect was examined via MTT and lactate dehydrogenase (LDH) assays. In addition, the PI3K inhibitor LY294002 was used to investigate the potential mechanism. JC-1 staining was used to detect the mitochondrial membrane potential (MMP), and western blotting (WB) was used to detect the phosphorylation of Akt-Ser473.
RESULTS
Compared with that in the control, the cell viability, total superoxide dismutase (SOD) activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly decreased, while the leakage rate of LDH was increased. And after treatment with 25 μM Res, the cell viability, total SOD activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly increased compared with those of the control cells, while the leakage rate of LDH was decreased. These effects of Res were antagonized by LY294002.
CONCLUSIONS
Res ameliorates 6-OHDA-induced damage to PC12 cells via activation of the PI3K/Akt signaling pathway.
目的
我们之前的研究发现，作为一种植物抗毒素的白藜芦醇（Res）通过激活大鼠体内的磷脂酰肌醇3激酶/蛋白激酶B（PI3K/Akt）信号通路，减轻了6-羟基多巴胺（6-OHDA）诱导的运动功能障碍。因此，我们进一步探讨了Res对6-OHDA诱导的PC12细胞损伤在PI3K/Akt信号通路上的保护作用。
方法
我们将PC12细胞与75μM的6-OHDA孵育24小时，然后加入终浓度为25μM的Res；通过MTT和乳酸脱氢酶（LDH）测定来检测保护作用。此外，使用PI3K抑制剂LY294002来研究潜在机制。采用JC-1染色检测线粒体膜电位（MMP），并使用蛋白质免疫印迹法（WB）检测Akt-Ser473的磷酸化。
结果
与对照组相比，6-OHDA处理的PC12细胞的细胞活力、总超氧化物歧化酶（SOD）活性、MMP和p-Akt-Ser473水平显著降低，而LDH泄漏率增加。用25μM Res处理后，与对照细胞相比，6-OHDA处理的PC12细胞的细胞活力、总SOD活性、MMP和p-Akt-Ser473水平显著增加，而LDH泄漏率降低。Res的这些作用被LY294002拮抗。
结论
Res通过激活PI3K/Akt信号通路改善6-OHDA诱导的PC12细胞损伤。
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