PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway

Li,Peng; Cao,Guiling

doi:10.3892/etm.2023.12343

PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway

Authors:
- Peng Li
- Guiling Cao
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Affiliations: Department of Neurology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China
Published online on: December 6, 2023 https://doi.org/10.3892/etm.2023.12343
Article Number: 55
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Human programmed cell death 4 (PDCD4) has been reported to participate in multiple neurological diseases. However, the role of PDCD4 in epilepsy, as well as its underlying mechanism, remains unclear. To induce excitotoxicity, 100 µM kainic acid (KA) was applied for the stimulation of HT22 cells for 12 h. Initially, the mRNA and protein expression levels of PDCD4 were evaluated using reverse transcription‑quantitative PCR and western blotting. A lactate dehydrogenase assay was performed to detect cell injury. Cell apoptosis was assessed using flow cytometry and western blotting was performed to determine the expression levels of apoptosis‑related proteins. Oxidative stress was detected using dichlorodihydrofluorescein diacetate staining, and malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH‑Px) assay kits. Furthermore, the expression levels of MAPK/NF‑κB signaling‑related proteins and endoplasmic reticulum (ER) stress‑related proteins C/EBP homologous protein, glucose‑regulated protein 78, activating transcription factor 4 and phosphorylated‑eukaryotic initiation factor‑2α were assessed by western blotting. It was revealed that PDCD4 expression was markedly elevated in KA‑induced HT22 cells, whereas PDCD4 silencing alleviated KA‑induced neurotoxicity of HT22 cells by alleviating cell injury and inhibiting apoptosis. In addition, PDCD4 silencing reduced the levels of reactive oxygen species and MDA, but elevated those of SOD and GSH‑Px. PDCD4 silencing also suppressed ER stress by blocking the MAPK/NF‑κB signaling pathway. By contrast, the MAPK agonist phorbol myristate acetate reversed the effects of PDCD4 silencing on KA‑induced neurotoxicity and oxidative stress in HT22 cells. In conclusion, PDCD4 silencing alleviated KA‑induced neurotoxicity and oxidative stress in HT22 cells by suppressing ER stress through the inhibition of the MAPK/NF‑κB signaling pathway, which may provide novel insights into the treatment of epilepsy.

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