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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Summary: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.
ISSN:2097-0927