TNFAIP1 Is Upregulated in APP/PS1 Mice and Promotes Apoptosis in SH-SY5Y Cells by Binding to RhoB
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TNFAIP1 Is Upregulated in APP/PS1 Mice and Promotes Apoptosis in SH‑SY5Y Cells by Binding to RhoB Ye Xiao1,2 · Yadan Li3 · Huihui Zhang1 · Liping Yang3 · Yinghua Jiang4 · Chenxi Wei2 · Xing Feng1 · Yu Xun2 · Shishan Yuan1 · Shuanglin Xiang2 · Ning Liu1,2 Received: 26 May 2020 / Accepted: 27 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Alzheimer’s disease (AD) poses a significant threat to human life and health. The intraneuronal accumulation of β-amyloid (Aβ) plaques in the brains of AD patients results in neuronal cell death, which is a key factor that triggers multiple changes in the pathogenesis of AD. The inhibition of Aβ-induced neuronal cell death may potentially help in the intervention and treatment of AD. Our previous study reported that tumor necrosis factor α-induced protein 1 (TNFAIP1) is induced by and promotes Aβ25–35-induced neurotoxicity in mouse neuronal cells, but the roles and regulatory mechanisms of TNFAIP1 are still largely unknown. In this study, our experimental results show that TNFAIP1 and p-TNFAIP1 (phosphorylation of TNFAIP1 at Ser280) are overexpressed in the neurons of the cortex and hippocampus in the brains of APP/PS1 mice, and the transcription factor NF-κB is involved in the Aβ-induced upregulation of TNFAIP1. Moreover, our results suggest that TNFAIP1 contributes to the Aβ-induced reactive oxygen species (ROS) production, decreased mitochondrial membrane potential (∆Ψm), and neuronal cell death in human SH-SY5Y cells. We further revealed that Aβ increases the binding of TNFAIP1 to RhoB, and knockdown of RhoB attenuates the TNFAIP1-induced apoptosis of human SH-SY5Y cells. These data suggest that TNFAIP1 is closely associated with AD pathogenesis, and overexpression of TNFAIP1 in the neurons of the brains of AD patients plays a role in apoptosis, at least in part, via RhoB signaling. Keywords Alzheimer’s disease · TNFAIP1 · Aβ · SH-SY5Y cells · RhoB
Ye Xiao and Yadan Li equally contributed to this work * Shishan Yuan [email protected]
Xing Feng [email protected]
* Shuanglin Xiang [email protected]
Yu Xun [email protected]
* Ning Liu [email protected]
1
Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of Medicine, Hunan Normal University, Changsha 410081, Hunan, China
2
State Key Laboratory of Developmental Biology of Freshwater Fish, School of Life Sciences, The National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, School of Life Sciences, Hunan Normal University, Changsha 410081, Hunan, China
3
Department of Environmental Science, Changsha Environmental Protection College, Changsha, Hunan 410004, P.R. China
4
Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Ye Xiao [email protected] Yadan Li [email protected] Huihui Zhang [email protected] Liping Yang [email protected] Yinghua Jiang [email protected] Chenxi Wei [email protected]
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