Dexmedetomidine Regulates Autophagy via the AMPK/mTOR Pathway to Improve SH-SY5Y-APP Cell Damage Induced by High Glucose.

IF 3.3 4区 医学 Q2 NEUROSCIENCES NeuroMolecular Medicine Pub Date : 2023-09-01 Epub Date: 2023-04-05 DOI:10.1007/s12017-023-08745-2
Pinzhong Chen, Xiaohui Chen, Honghong Zhang, Jianghu Chen, Mingxue Lin, Haitao Qian, Fei Gao, Yisheng Chen, Cansheng Gong, Xiaochun Zheng, Ting Zheng
{"title":"Dexmedetomidine Regulates Autophagy via the AMPK/mTOR Pathway to Improve SH-SY5Y-APP Cell Damage Induced by High Glucose.","authors":"Pinzhong Chen,&nbsp;Xiaohui Chen,&nbsp;Honghong Zhang,&nbsp;Jianghu Chen,&nbsp;Mingxue Lin,&nbsp;Haitao Qian,&nbsp;Fei Gao,&nbsp;Yisheng Chen,&nbsp;Cansheng Gong,&nbsp;Xiaochun Zheng,&nbsp;Ting Zheng","doi":"10.1007/s12017-023-08745-2","DOIUrl":null,"url":null,"abstract":"<p><p>Neurodegenerative diseases and postoperative cognitive dysfunction involve the accumulation of β-amyloid peptide (Aβ). High glucose can inhibit autophagy, which facilitates intracellular Aβ clearance. The α2-adrenoreceptor agonist dexmedetomidine (DEX) can provide neuroprotection against several neurological diseases; however, the mechanism remains unclear. This study investigated whether DEX regulated autophagy via the AMPK/mTOR pathway to improve high glucose-induced neurotoxicity in SH-SY5Y/APP695 cells. SH-SY5Y/APP695 cells were cultured with high glucose with/without DEX. To examine the role of autophagy, the autophagy activator rapamycin (RAPA) and autophagy inhibitor 3-methyladenine (3-MA) were used. The selective AMPK inhibitor compound C was used to investigate the involvement of the AMPK pathway. Cell viability and apoptosis were examined by CCK-8 and annexin V-FITC/PI flow cytometric assays, respectively. Autophagy was analyzed by monodansylcadaverine staining of autophagic vacuoles. Autophagy- and apoptosis-related protein expression and the phosphorylation levels of AMPK/mTOR pathway molecules were quantified by western blotting. DEX pretreatment significantly suppressed high glucose-induced neurotoxicity in SH-SY5Y/APP695 cells, as evidenced by the enhanced viability, restoration of cellular morphology, and reduction in apoptotic cells. Furthermore, RAPA had a protective effect similar to that of DEX, but 3-MA eliminated the protective effect of DEX by promoting mTOR activation. Moreover, the AMPK/mTOR pathway was involved in DEX-mediated autophagy. Compound C significantly suppressed autophagy and reversed the protective effect of DEX against high glucose in SH-SY5Y/APP695 cells. Our findings demonstrated that DEX protected SH-SY5Y/APP695 cells against high glucose-induced neurotoxicity by upregulating autophagy through the AMPK/mTOR pathway, suggesting a role of DEX in treating POCD in diabetic patients.</p>","PeriodicalId":19304,"journal":{"name":"NeuroMolecular Medicine","volume":" ","pages":"415-425"},"PeriodicalIF":3.3000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"NeuroMolecular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12017-023-08745-2","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/4/5 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0

Abstract

Neurodegenerative diseases and postoperative cognitive dysfunction involve the accumulation of β-amyloid peptide (Aβ). High glucose can inhibit autophagy, which facilitates intracellular Aβ clearance. The α2-adrenoreceptor agonist dexmedetomidine (DEX) can provide neuroprotection against several neurological diseases; however, the mechanism remains unclear. This study investigated whether DEX regulated autophagy via the AMPK/mTOR pathway to improve high glucose-induced neurotoxicity in SH-SY5Y/APP695 cells. SH-SY5Y/APP695 cells were cultured with high glucose with/without DEX. To examine the role of autophagy, the autophagy activator rapamycin (RAPA) and autophagy inhibitor 3-methyladenine (3-MA) were used. The selective AMPK inhibitor compound C was used to investigate the involvement of the AMPK pathway. Cell viability and apoptosis were examined by CCK-8 and annexin V-FITC/PI flow cytometric assays, respectively. Autophagy was analyzed by monodansylcadaverine staining of autophagic vacuoles. Autophagy- and apoptosis-related protein expression and the phosphorylation levels of AMPK/mTOR pathway molecules were quantified by western blotting. DEX pretreatment significantly suppressed high glucose-induced neurotoxicity in SH-SY5Y/APP695 cells, as evidenced by the enhanced viability, restoration of cellular morphology, and reduction in apoptotic cells. Furthermore, RAPA had a protective effect similar to that of DEX, but 3-MA eliminated the protective effect of DEX by promoting mTOR activation. Moreover, the AMPK/mTOR pathway was involved in DEX-mediated autophagy. Compound C significantly suppressed autophagy and reversed the protective effect of DEX against high glucose in SH-SY5Y/APP695 cells. Our findings demonstrated that DEX protected SH-SY5Y/APP695 cells against high glucose-induced neurotoxicity by upregulating autophagy through the AMPK/mTOR pathway, suggesting a role of DEX in treating POCD in diabetic patients.

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
右美托咪定通过AMPK/mTOR途径调节自噬以改善高糖诱导的SH-SY5Y-APP细胞损伤。
神经退行性疾病和术后认知功能障碍涉及β-淀粉样肽(Aβ)的积累。高糖可以抑制自噬,从而促进细胞内Aβ的清除。α2-肾上腺素受体激动剂右美托咪定(DEX)可以对几种神经疾病提供神经保护;然而,其机制尚不清楚。本研究探讨了DEX是否通过AMPK/mTOR途径调节自噬,以改善SH-SY5Y/APP695细胞中高糖诱导的神经毒性。SH-SY5Y/APP695细胞在有/无DEX的高糖下培养。为了检测自噬的作用,使用了自噬激活剂雷帕霉素(RAPA)和自噬抑制剂3-甲基腺嘌呤(3-MA)。使用选择性AMPK抑制剂化合物C来研究AMPK途径的参与。分别用CCK-8和annexin V-FITC/PI流式细胞仪检测细胞活力和细胞凋亡。通过自噬液泡的单丹酰尸胺染色来分析自噬。自噬和凋亡相关蛋白的表达以及AMPK/mTOR通路分子的磷酸化水平通过蛋白质印迹进行定量。DEX预处理显著抑制了SH-SY5Y/APP695细胞中高糖诱导的神经毒性,表现为活力增强、细胞形态恢复和凋亡细胞减少。此外,RAPA具有与DEX类似的保护作用,但3-MA通过促进mTOR激活来消除DEX的保护作用。此外,AMPK/mTOR通路参与了DEX介导的自噬。化合物C显著抑制SH-SY5Y/APP695细胞中的自噬并逆转DEX对高糖的保护作用。我们的研究结果表明,DEX通过AMPK/mTOR途径上调自噬,保护SH-SY5Y/APP695细胞对抗高糖诱导的神经毒性,表明DEX在治疗糖尿病患者POCD中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
NeuroMolecular Medicine
NeuroMolecular Medicine 医学-神经科学
CiteScore
7.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: NeuroMolecular Medicine publishes cutting-edge original research articles and critical reviews on the molecular and biochemical basis of neurological disorders. Studies range from genetic analyses of human populations to animal and cell culture models of neurological disorders. Emerging findings concerning the identification of genetic aberrancies and their pathogenic mechanisms at the molecular and cellular levels will be included. Also covered are experimental analyses of molecular cascades involved in the development and adult plasticity of the nervous system, in neurological dysfunction, and in neuronal degeneration and repair. NeuroMolecular Medicine encompasses basic research in the fields of molecular genetics, signal transduction, plasticity, and cell death. The information published in NEMM will provide a window into the future of molecular medicine for the nervous system.
期刊最新文献
Time of the Day of Traumatic Brain Injury has Minimal Effects on Behavioral and Histological Outcomes in Mice of Both Sexes. Seipin Deficiency Impairs Motor Coordination in Mice by Compromising Spinal Cord Myelination. Bacopa monnieri Extract Diminish Hypoxia-Induced Anxiety by Regulating HIF-1α Signaling and Enhancing the Antioxidant Defense System in Hippocampus. From Gut to Brain: The Impact of Short-Chain Fatty Acids on Brain Cancer. Association of IL6 Gene Polymorphisms and Neurological Disorders: Insights from Integrated Bioinformatics and Meta-Analysis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1