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大麻二酚通过上调SIRT1以抑制NF-κB和NOTCH信号通路诱导自噬,从而保护神经细胞免受线粒体功能障碍的影响。

Cannabidiol Induces Autophagy to Protects Neural Cells From Mitochondrial Dysfunction by Upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways.

作者信息

Kang Shaolei, Li Jinglin, Yao Zhihui, Liu Jiaxin

机构信息

Department of Radiology, The First Affiliated Hospital of Kunming Medical University, Kunming, China.

Medical School, Kunming University of Science and Technology, Kunming, China.

出版信息

Front Cell Neurosci. 2021 Mar 30;15:654340. doi: 10.3389/fncel.2021.654340. eCollection 2021.

Abstract

The protective effect of Cannabidiol on Parkinson's disease (PD) has been found in recent study. However, the specific mechanism of the protective effect of Cannabidiol on PD nerve damage require further exploration. This study aims to investigate effect of Cannabidiol on MMP-induced Neural Cells (SH-SY5Y) mitochondrial dysfunction. MMP and Cannabidiol were used to treat SH-SY5Y cells, the cells viability was measured by MTT assay. The expression of Tyrosine hydroxylase (TH) in cells was measured by western blotting and Immunofluorescence staining. The relationship among Cannabidiol, Silent mating type information regulation 2 homolog-1 (SIRT1) and NOTCH signaling, NF-κB signaling was examined by western blotting. The effect of Cannabidiol on MMP-induced mitochondrial dysfunction of SH-SY5Y cells was measured by western blotting. Cannabidiol alleviated loss of TH expression and cytotoxicity in the MPP-induced SH-SY5Y cells. Further mechanistic investigation showed that Cannabidiol induced SH-SY5Y cells autophagy to protects cells from mitochondrial dysfunction by upregulating SIRT1 to Inhibits NF-κB and NOTCH Pathways. Taken together, Cannabidiol acts as a protector in PD.

摘要

近期研究发现大麻二酚对帕金森病(PD)具有保护作用。然而,大麻二酚对PD神经损伤保护作用的具体机制尚需进一步探索。本研究旨在探讨大麻二酚对线粒体膜电位(MMP)诱导的神经细胞(SH-SY5Y)线粒体功能障碍的影响。用MMP和大麻二酚处理SH-SY5Y细胞,采用MTT法检测细胞活力。通过蛋白质免疫印迹法和免疫荧光染色法检测细胞中酪氨酸羟化酶(TH)的表达。通过蛋白质免疫印迹法检测大麻二酚、沉默信息调节因子2同源物1(SIRT1)与NOTCH信号通路、NF-κB信号通路之间的关系。通过蛋白质免疫印迹法检测大麻二酚对MMP诱导的SH-SY5Y细胞线粒体功能障碍的影响。大麻二酚减轻了MPP诱导的SH-SY5Y细胞中TH表达的缺失和细胞毒性。进一步的机制研究表明,大麻二酚通过上调SIRT1以抑制NF-κB和NOTCH通路,诱导SH-SY5Y细胞自噬,从而保护细胞免受线粒体功能障碍的影响。综上所述,大麻二酚在PD中起到保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6bd4/8042325/48481d722719/fncel-15-654340-g001.jpg

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