Scavenging Reactive Oxygen Species Decreases Amyloid-beta Levels via Activation of PI3K/Akt/GLUT1 Pathway in N2a/APP695swe Cells

作者全名："Peng, Yan; Zhang, Li; Zhou, Fanlin; Wang, Yangyang; Zhang, Xiong; Fan, Jianing; Li, Shijie; Li, Xiaoju; Li, Yu"

作者地址："[Peng, Yan; Zhang, Xiong; Li, Yu] Chongqing Med Univ, Sch Basic Med, Inst Neurosci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Zhang, Li] Chongqing Med Univ, Dept Pathophysiol, Chongqing, Peoples R China; [Zhou, Fanlin; Wang, Yangyang; Fan, Jianing; Li, Shijie; Li, Xiaoju; Li, Yu] Chongqing Univ Canc Hosp, Dept Pathol, Chongqing, Peoples R China; [Zhou, Fanlin; Wang, Yangyang; Fan, Jianing; Li, Shijie; Li, Xiaoju; Li, Yu] Chongqing Canc Inst, Chongqing, Peoples R China; [Zhou, Fanlin; Wang, Yangyang; Fan, Jianing; Li, Shijie; Li, Xiaoju; Li, Yu] Chongqing Canc Hosp, Chongqing, Peoples R China"

通信作者："Li, Y (通讯作者)，Chongqing Med Univ, Sch Basic Med, Inst Neurosci, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF ALZHEIMERS DISEASE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000878428800014

JCR分区：Q2

影响因子：4

年份：2022

卷号：90

期号：1

开始页：185

结束页：198

文献类型：Article

关键词：Alzheimer's disease; glucose uptake; GLUT1; PI3K/Akt; reactive oxygen species

摘要："Background: Dysregulated glucose metabolism in the brain is considered to be one of the key causes of Alzheimer's disease (AD). Abnormal glucose uptake in AD is tightly associated with decreased levels of glucose transporter 1 (GLUT1) and GLUT3 in the brain, but the underlying mechanisms remain unclear. Objective: We aimed to explore the cause and mechanism of impaired glucose uptake in AD. Methods: N2a/WT and N2a/APP695swe cells were cultured in vitro, and cellular glucose uptake and ATP content, as well as the expression of GLUT1, GLUT3, and PI3K/Akt pathway members, were detected. Intracellular reactive oxygen species (ROS) levels were detected by flow cytometry. After treatment with the ROS scavenger N-acetyl-L-cysteine (NAC), the above indicators were detected again. Results: GLUT1 expressionwas significantly decreased (p = 0.0138) in N2a/APP695swe cells, while GLUT3 expressionwas no statistical difference (p > 0.05). After NAC treatment, PI3K and Akt phosphorylation levels, GLUT1 expression, glucose uptake and ATP levels were remarkably increased (p = 0.0006, p = 0.0008, p = 0.0009, p = 0.0001, p = 0.0013), whileA beta levels were significantly decreased (p = 0.0058, p = 0.0066). After addition of the PI3K inhibitor LY29004, GLUT1 expression was reduced (p = 0.0008), and A beta levels were increased (p = 0.0009, p = 0.0117). In addition, increases in glucose uptake and ATP levels induced by the Akt activator SC79 were hindered by the GLUT1 inhibitor WZB117 (p = 0.0002, p = 0.0005). A beta levels were decreased after SC79 treatment and increased after WZB117 treatment (p = 0.0212, p = 0.0006). Conclusion: Taken together, scavenging of ROS prevents from A beta deposition via activation of the PI3K/Akt/GLUT1 pathway, and improved the impaired glucose uptake in N2a/APP695swe cells."

基金机构：National Natural Science Foundation of China [NSFC: 81671261]; Natural Science Foundation of Chongqing [cstc2017jcyjAX0050]; Performance Incentive Guidance for Scientific Research Institution of Chongqing [cstc2020jxjl0085]; Fundamental Research Funds for the Central Universities [2019CDYGZD002]

基金资助正文："Thanks to all the members of our research team for the constructive discussion and suggestions that shaped this work. This work was supported by the National Natural Science Foundation of China (NSFC: 81671261), the Natural Science Foundation of Chongqing (No. cstc2017jcyjAX0050), the Performance Incentive Guidance for Scientific Research Institution of Chongqing (No. cstc2020jxjl0085) and Fundamental Research Funds for the Central Universities (No. 2019CDYGZD002)."