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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
    Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 55
    |
    Published online on: December 6, 2023
       https://doi.org/10.3892/etm.2023.12343
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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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1 

Thijs RD, Surges R, O'Brien TJ and Sander JW: Epilepsy in adults. Lancet. 393:689–701. 2019.PubMed/NCBI View Article : Google Scholar

2 

Manford M: Recent advances in epilepsy. J Neurol. 264:1811–1824. 2017.PubMed/NCBI View Article : Google Scholar

3 

Steriade C, Titulaer MJ, Vezzani A, Sander JW and Thijs RD: The association between systemic autoimmune disorders and epilepsy and its clinical implications. Brain. 144:372–390. 2021.PubMed/NCBI View Article : Google Scholar

4 

Bartolini E, Ferrari AR, Lattanzi S, Pradella S and Zaccara G: Drug-resistant epilepsy at the age extremes: Disentangling the underlying etiology. Epilepsy Behav. 132(108739)2022.PubMed/NCBI View Article : Google Scholar

5 

Engel J Jr: Evolution of concepts in epilepsy surgery. Epileptic Disord. 21:391–409. 2019.PubMed/NCBI View Article : Google Scholar

6 

Guerrini R, Balestrini S, Wirrell EC and Walker MC: Monogenic epilepsies: Disease mechanisms, clinical phenotypes, and targeted therapies. Neurology. 97:817–831. 2021.PubMed/NCBI View Article : Google Scholar

7 

Asadi-Pooya AA and Farazdaghi M: Definition of drug-resistant epilepsy: A reappraisal based on epilepsy types. Acta Neurol Scand. 145:627–632. 2022.PubMed/NCBI View Article : Google Scholar

8 

Zhang L and Wang Y: Gene therapy in epilepsy. Biomed Pharmacother. 143(112075)2021.PubMed/NCBI View Article : Google Scholar

9 

Lin W, Qian X, Yang LK, Zhu J, Wang D, Hang CH, Wang Y and Chen T: Inhibition of miR-134-5p protects against kainic acid-induced excitotoxicity through Sirt3-mediated preservation of mitochondrial function. Epilepsy Res. 176(106722)2021.PubMed/NCBI View Article : Google Scholar

10 

Dong X, Fan J, Lin D, Wang X, Kuang H, Gong L, Chen C, Jiang J, Xia N, He D, et al: Captopril alleviates epilepsy and cognitive impairment by attenuation of C3-mediated inflammation and synaptic phagocytosis. J Neuroinflammation. 19(226)2022.PubMed/NCBI View Article : Google Scholar

11 

Xiao Z, Peng J, Yang L, Kong H and Yin F: Interleukin-1β plays a role in the pathogenesis of mesial temporal lobe epilepsy through the PI3K/Akt/mTOR signaling pathway in hippocampal neurons. J Neuroimmunol. 282:110–117. 2015.PubMed/NCBI View Article : Google Scholar

12 

Qiu X, Cao L, Yang X, Zhao X, Liu X, Han Y, Xue Y, Jiang H and Chi Z: Role of mitochondrial fission in neuronal injury in pilocarpine-induced epileptic rats. Neuroscience. 245:157–165. 2013.PubMed/NCBI View Article : Google Scholar

13 

Xie N, Wang C, Wu C, Cheng X, Gao Y, Zhang H, Zhang Y and Lian Y: Mdivi-1 protects epileptic hippocampal neurons from apoptosis via inhibiting oxidative stress and endoplasmic reticulum stress in vitro. Neurochem Res. 41:1335–1342. 2016.PubMed/NCBI View Article : Google Scholar

14 

Gao Y, Luo C, Yao Y, Huang J, Fu H, Xia C, Ye G, Yu L, Han J, Fan Y and Tao L: IL-33 alleviated brain damage via anti-apoptosis, endoplasmic reticulum stress, and inflammation after epilepsy. Front Neurosci. 14(898)2020.PubMed/NCBI View Article : Google Scholar

15 

Matsuhashi S, Manirujjaman M, Hamajima H and Ozaki I: Control mechanisms of the tumor suppressor PDCD4: Expression and functions. Int J Mol Sci. 20(2304)2019.PubMed/NCBI View Article : Google Scholar

16 

Cai Q, Yang HS, Li YC and Zhu J: Dissecting the roles of PDCD4 in breast cancer. Front Oncol. 12(855807)2022.PubMed/NCBI View Article : Google Scholar

17 

Shan W, Ge H, Chen B, Huang L, Zhu S and Zhou Y: Upregulation of miR-499a-5p decreases cerebral ischemia/reperfusion injury by targeting PDCD4. Cell Mol Neurobiol. 42:2157–2170. 2022.PubMed/NCBI View Article : Google Scholar

18 

Di Paolo A, Eastman G, Mesquita-Ribeiro R, Farias J, Macklin A, Kislinger T, Colburn N, Munroe D, Sotelo Sosa JR, Dajas-Bailador F and Sotelo-Silveira JR: PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses. RNA. 26:1637–1653. 2020.PubMed/NCBI View Article : Google Scholar

19 

Peng C, Zhang C, Su Z and Lin D: DGCR5 attenuates neuropathic pain through sponging miR-330-3p and regulating PDCD4 in CCI rat models. J Cell Physiol. 234:7292–7300. 2019.PubMed/NCBI View Article : Google Scholar

20 

Zheng XY, Zhang HL, Luo Q and Zhu J: Kainic acid-induced neurodegenerative model: Potentials and limitations. J Biomed Biotechnol. 2011(457079)2011.PubMed/NCBI View Article : Google Scholar

21 

Ullah I, Park HY and Kim MO: Anthocyanins protect against kainic acid-induced excitotoxicity and apoptosis via ROS-activated AMPK pathway in hippocampal neurons. CNS Neurosci Ther. 20:327–338. 2014.PubMed/NCBI View Article : Google Scholar

22 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

23 

Myers KA: Genetic epilepsy syndromes. Continuum (Minneap Minn). 28:339–362. 2022.PubMed/NCBI View Article : Google Scholar

24 

Fisher RS: Redefining epilepsy. Curr Opin Neurol. 28:130–135. 2015.PubMed/NCBI View Article : Google Scholar

25 

Cui H, Wang Q, Lei Z, Feng M, Zhao Z, Wang Y and Wei G: DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation. J Exp Clin Cancer Res. 38(350)2019.PubMed/NCBI View Article : Google Scholar

26 

Chen Q, Lu H, Duan C, Zhu X, Zhang Y, Li M and Zhang D: PDCD4 simultaneously promotes microglia activation via PDCD4-MAPK-NF-κB positive loop and facilitates neuron apoptosis during neuroinflammation. Inflammation. 45:234–252. 2022.PubMed/NCBI View Article : Google Scholar

27 

Wang Y and Chang Q: MicroRNA miR-212 regulates PDCD4 to attenuate Aβ25-35-induced neurotoxicity via PI3K/AKT signaling pathway in Alzheimer's disease. Biotechnol Lett. 42:1789–1797. 2020.PubMed/NCBI View Article : Google Scholar

28 

Zhao Y and Ai Y: Knockdown of lncRNA MALAT1 alleviates bupivacaine-induced neurotoxicity via the miR-101-3p/PDCD4 axis. Life Sci. 232(116606)2019.PubMed/NCBI View Article : Google Scholar

29 

Zhang J, Han Y, Zhao Y, Li Q, Jin H and Qin J: Inhibition of TRIB3 protects against neurotoxic injury induced by kainic acid in rats. Front Pharmacol. 10(585)2019.PubMed/NCBI View Article : Google Scholar

30 

Li M, Cui L, Feng X, Wang C, Zhang Y, Wang L, Ding Y and Zhao T: Losmapimod protected epileptic rats from hippocampal neuron damage through inhibition of the MAPK pathway. Front Pharmacol. 10(625)2019.PubMed/NCBI View Article : Google Scholar

31 

Qi Y, Qian R, Jia L, Fei X, Zhang D, Zhang Y, Jiang S and Fu X: Overexpressed microRNA-494 represses RIPK1 to attenuate hippocampal neuron injury in epilepsy rats by inactivating the NF-κB signaling pathway. Cell Cycle. 19:1298–1313. 2020.PubMed/NCBI View Article : Google Scholar

32 

Yuan M and Yuan B: Antidepressant-like effects of rehmannioside A on rats induced by chronic unpredictable mild stress through inhibition of endoplasmic reticulum stress and apoptosis of hippocampus. J Chem Neuroanat. 125(102157)2022.PubMed/NCBI View Article : Google Scholar

33 

Chen F, Zhu J and Wang W: Ulinastatin attenuates LPS-induced inflammation and inhibits endoplasmic reticulum stress-induced apoptosis in renal tubular epithelial cells via regulation of the TLR4/NF-κB and Nrf2/HO-1 pathways. Inflammation. 44:2323–2332. 2021.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Li P and Cao G: PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway. Exp Ther Med 27: 55, 2024.
APA
Li, P., & Cao, G. (2024). PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway. Experimental and Therapeutic Medicine, 27, 55. https://doi.org/10.3892/etm.2023.12343
MLA
Li, P., Cao, G."PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway". Experimental and Therapeutic Medicine 27.2 (2024): 55.
Chicago
Li, P., Cao, G."PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway". Experimental and Therapeutic Medicine 27, no. 2 (2024): 55. https://doi.org/10.3892/etm.2023.12343
Copy and paste a formatted citation
x
Spandidos Publications style
Li P and Cao G: PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway. Exp Ther Med 27: 55, 2024.
APA
Li, P., & Cao, G. (2024). PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway. Experimental and Therapeutic Medicine, 27, 55. https://doi.org/10.3892/etm.2023.12343
MLA
Li, P., Cao, G."PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway". Experimental and Therapeutic Medicine 27.2 (2024): 55.
Chicago
Li, P., Cao, G."PDCD4 silencing alleviates KA‑induced neurotoxicity of HT22 cells by inhibiting endoplasmic reticulum stress via blocking the MAPK/NF‑κB signaling pathway". Experimental and Therapeutic Medicine 27, no. 2 (2024): 55. https://doi.org/10.3892/etm.2023.12343
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