Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory response

Objective To study the role and mechanisms of equilibrative nucleotide transporter 1 (ENT1) on Alzheimer's disease (AD) by constructing ENT1 overexpression and knockdown plasmids. Methods Molecular cloning was used to construct the ENT1 overexpression (pAAV-ENT1-mCherry) and knockdown (pAAV-EN...

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Main Authors: ZHANG Xiaoyuan, MA Ziteng, JIA Yunfang
Format: Article
Language:zho
Published: Editorial Office of Journal of Army Medical University 2024-12-01
Series:陆军军医大学学报
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Online Access:https://aammt.tmmu.edu.cn/html/202403052.htm
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author ZHANG Xiaoyuan
MA Ziteng
JIA Yunfang
author_facet ZHANG Xiaoyuan
MA Ziteng
JIA Yunfang
author_sort ZHANG Xiaoyuan
collection DOAJ
description Objective To study the role and mechanisms of equilibrative nucleotide transporter 1 (ENT1) on Alzheimer's disease (AD) by constructing ENT1 overexpression and knockdown plasmids. Methods Molecular cloning was used to construct the ENT1 overexpression (pAAV-ENT1-mCherry) and knockdown (pAAV-ENT1shRNA-ZsGreen) plasmids. The overexpression plasmids and the knockdown plasmids were transfected into N2A cells (mouse Neuro A2 cells) and N2A-APP cells (N2A cells stably expressing human APP695). The expression of ENT1 and inflammatory factors at mRNA and protein levels were detected by real-time qPCR and Western blotting, respectively, and the change in cell viability were measured with CCK-8 assay. Results Sequencing and real-time qPCR indicated that ENT1 overexpression and knockdown plasmids were successfully constructed. CCK-8 assay showed that ENT1 overexpression significantly reduced the cell survival rate within 24 h (P < 0.05), while its knockdown increased the cell survival rate (P < 0.01). Real-time qPCR displayed that overexpression of ENT1 enhanced the expression levels of inflammatory factors, such as IL-1β, TNF-α, C1q-a and C1q-b in N2A cells (P < 0.05), while ENT1 knockdown reversed the above changes in inflammatory factors in N2A-APP cells (P < 0.05). Conclusion Knockdown of ENT1 attenuates pathological changes in AD by reducing the inflammatory response. ENT1 may be a potential target in the pathological mechanism of AD.
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record_format Article
series 陆军军医大学学报
spelling doaj-art-fb6a64c6b4cc4318924f6a95da74959f2024-12-16T01:15:14ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272024-12-0146232588259810.16016/j.2097-0927.202403052Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory responseZHANG Xiaoyuan0MA Ziteng1JIA Yunfang2Neuroscience Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaNeuroscience Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, ChinaNeuroscience Center, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China Objective To study the role and mechanisms of equilibrative nucleotide transporter 1 (ENT1) on Alzheimer's disease (AD) by constructing ENT1 overexpression and knockdown plasmids. Methods Molecular cloning was used to construct the ENT1 overexpression (pAAV-ENT1-mCherry) and knockdown (pAAV-ENT1shRNA-ZsGreen) plasmids. The overexpression plasmids and the knockdown plasmids were transfected into N2A cells (mouse Neuro A2 cells) and N2A-APP cells (N2A cells stably expressing human APP695). The expression of ENT1 and inflammatory factors at mRNA and protein levels were detected by real-time qPCR and Western blotting, respectively, and the change in cell viability were measured with CCK-8 assay. Results Sequencing and real-time qPCR indicated that ENT1 overexpression and knockdown plasmids were successfully constructed. CCK-8 assay showed that ENT1 overexpression significantly reduced the cell survival rate within 24 h (P < 0.05), while its knockdown increased the cell survival rate (P < 0.01). Real-time qPCR displayed that overexpression of ENT1 enhanced the expression levels of inflammatory factors, such as IL-1β, TNF-α, C1q-a and C1q-b in N2A cells (P < 0.05), while ENT1 knockdown reversed the above changes in inflammatory factors in N2A-APP cells (P < 0.05). Conclusion Knockdown of ENT1 attenuates pathological changes in AD by reducing the inflammatory response. ENT1 may be a potential target in the pathological mechanism of AD. https://aammt.tmmu.edu.cn/html/202403052.htmequilibrative nucleotide transporter 1alzheimer's diseaseinflammatory factorcell viability
spellingShingle ZHANG Xiaoyuan
MA Ziteng
JIA Yunfang
Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory response
陆军军医大学学报
equilibrative nucleotide transporter 1
alzheimer's disease
inflammatory factor
cell viability
title Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory response
title_full Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory response
title_fullStr Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory response
title_full_unstemmed Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory response
title_short Knockdown of equilibrative nucleotide transporter 1 protects against Alzheimer's disease by reducing inflammatory response
title_sort knockdown of equilibrative nucleotide transporter 1 protects against alzheimer s disease by reducing inflammatory response
topic equilibrative nucleotide transporter 1
alzheimer's disease
inflammatory factor
cell viability
url https://aammt.tmmu.edu.cn/html/202403052.htm
work_keys_str_mv AT zhangxiaoyuan knockdownofequilibrativenucleotidetransporter1protectsagainstalzheimersdiseasebyreducinginflammatoryresponse
AT maziteng knockdownofequilibrativenucleotidetransporter1protectsagainstalzheimersdiseasebyreducinginflammatoryresponse
AT jiayunfang knockdownofequilibrativenucleotidetransporter1protectsagainstalzheimersdiseasebyreducinginflammatoryresponse