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白藜芦醇通过增强SIRT1介导的自噬抑制脂多糖诱导的VSC4.1运动神经元凋亡。

Resveratrol inhibits LPS-induced apoptosis in VSC4.1 motoneurons through enhancing SIRT1-mediated autophagy.

作者信息

Tian He, Zhao Haosen, Mei Xifan, Li Daoyong, Lin Jiaquan, Lin Sen, Song Changwei

机构信息

Department of Histology and Embryology, School of Basic Medicine, Jinzhou Medical University, Liaoning 121000, China.

Department of Orthopedics, First Affiliated Hospital of Jinzhou Medical University, Liaoning 121000, China.

出版信息

Iran J Basic Med Sci. 2021 Jan;24(1):38-43. doi: 10.22038/ijbms.2020.44534.10416.

Abstract

OBJECTIVES

Resveratrol has been recognized as a potential therapeutic drug in spinal cord injury (SCI). Sirtuin 1 (SIRT1) is vital in the regulation of apoptosis and cell stress response. In this research, our purpose was to explore the mechanisms of resveratrol on neuroprotection and to explore the role of SIRT1.

MATERIALS AND METHODS

We used lipopolysaccharide (LPS) in the VSC4.1 spinal cord neuron cell line to mimic the micro-environment of the injured spinal cord. The apoptosis of VSC4.1 motoneurons was assessed by TUNEL staining, Western blot, and RT-PCR. Immunofluorescence staining was used to observe the expression site of SIRT1, LC3-B, and Beclin-1, and their protein levels were measured by Western blot and RT-PCR.

RESULTS

Our results showed that resveratrol inhibits LPS-induced apoptosis in VSC4.1 motoneurons. Levels of LC3-B, beclin-1, and SIRT1 indicated a significant increase after resveratrol treatment. But, if autophagy was inhibited, apoptosis in VSC4.1 motoneurons significantly increased. When the cells were treated with EX527, a SIRT1 inhibitor, the protein contents of LC3-B and Beclin-1 were suppressed.

CONCLUSION

Resveratrol inhibits apoptosis through promoting autophagy in VSC4.1 motoneurons. SIRT1 was involved in autophagy activated by resveratrol in VSC4.1 motoneurons.

摘要

目的

白藜芦醇已被公认为脊髓损伤(SCI)的一种潜在治疗药物。沉默调节蛋白1(SIRT1)在细胞凋亡和细胞应激反应的调节中至关重要。在本研究中,我们的目的是探讨白藜芦醇的神经保护机制,并探究SIRT1的作用。

材料与方法

我们在VSC4.1脊髓神经元细胞系中使用脂多糖(LPS)来模拟脊髓损伤的微环境。通过TUNEL染色、蛋白质印迹法和逆转录聚合酶链反应(RT-PCR)评估VSC4.1运动神经元的凋亡情况。采用免疫荧光染色观察SIRT1、微管相关蛋白1轻链3β(LC3-B)和自噬相关蛋白1(Beclin-1)的表达位点,并通过蛋白质印迹法和RT-PCR检测它们的蛋白质水平。

结果

我们的结果表明,白藜芦醇可抑制LPS诱导的VSC4.1运动神经元凋亡。白藜芦醇处理后,LC3-B、Beclin-1和SIRT1的水平显著升高。但是,如果自噬被抑制,VSC4.1运动神经元的凋亡则显著增加。当用SIRT1抑制剂EX527处理细胞时,LC3-B和Beclin-1的蛋白质含量受到抑制。

结论

白藜芦醇通过促进VSC4.1运动神经元的自噬来抑制凋亡。SIRT1参与了白藜芦醇在VSC4.1运动神经元中激活的自噬过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/62dc/7894637/652aaa6e14c6/IJBMS-24-038-g001.jpg

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