Downregulation of TNFAIP1 alleviates OGD/R‑induced neuronal damage by suppressing Nrf2/GPX4‑mediated ferroptosis

Xiong,Lie; Zhang,Jingruo; Shi,Hanqiang; Zhu,Gaofeng; Ji,Xiaoyan; Li,Mengjiao; Zhu,Ping; Luo,Kaitao

doi:10.3892/etm.2022.11724

Downregulation of TNFAIP1 alleviates OGD/R‑induced neuronal damage by suppressing Nrf2/GPX4‑mediated ferroptosis

Authors:
- Lie Xiong
- Jingruo Zhang
- Hanqiang Shi
- Gaofeng Zhu
- Xiaoyan Ji
- Mengjiao Li
- Ping Zhu
- Kaitao Luo
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Affiliations: Central Laboratory, Zhejiang Chinese Medical University‑Affiliated Jiaxing Traditional Chinese Medicine Hospital, Jiaxing, Zhejiang 314001, P.R. China, Department of Acupuncture, Zhejiang Chinese Medical University‑Affiliated Jiaxing Traditional Chinese Medicine Hospital, Jiaxing, Zhejiang 314001, P.R. China, Department of Neurosurgery, Zhejiang Chinese Medical University‑Affiliated Jiaxing Traditional Chinese Medicine Hospital, Jiaxing, Zhejiang 314001, P.R. China
Published online on: November 23, 2022 https://doi.org/10.3892/etm.2022.11724
Article Number: 25
Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

TNFα‑induced protein 1 (TNFAIP1) serve a role in neurovascular disease. However, the potential role and molecular mechanism of TNFAIP1 in cerebral ischemia‑reperfusion (I/R) remains elusive. In the present study, reverse transcription‑quantitative PCR and western blotting were used to assess TNFAIP1 mRNA and protein expression levels in PC12 cells. Furthermore, using Cell Counting Kit‑8, flow cytometry and western blotting, cell viability and apoptosis were evaluated. Oxidative stress was evaluated using DCFH‑DA staining and ELISA was used for assessment of inflammatory factors. Expression of components in the nuclear factor erythroid 2‑related factor 2 (Nrf2) signaling pathway and ferroptosis were assessed using western blotting analysis and an iron assay kit. TNFAIP1 expression was significantly upregulated in oxygen glucose deprivation and reperfusion (OGD/R)‑injured PC12 cells. However, knocking down TNFAIP1 expression restored PC12 cell viability and decreased apoptosis following OGD/R‑challenge. Furthermore, TNFAIP1 silencing significantly suppressed OGD/R‑induced oxidative stress and inflammatory damage in PC12 cells. TNFAIP1 knockdown inhibited ferroptosis via activation of the Nrf2 signaling pathway in OGD/R‑injured PC12 cells. Erastin treatment reversed the beneficial effects of TNFAIP1 knockdown on PC12 cell viability, apoptosis alleviation, oxidative stress and inflammation following OGD/R treatment. These results suggested that TNFAIP1 knockdown could alleviate OGD/R‑induced neuronal cell damage by suppressing Nrf2‑mediated ferroptosis, which might lay the foundation for the investigation of targeted‑therapy for cerebral I/R injury in clinic.

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