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October 2014 Volume 10 Issue 4

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Article

Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons

  • Authors:
    • Xue‑Wen Liu
    • En‑Fei Ji
    • Peng He
    • Rui‑Xian Xing
    • Bu‑Xian Tian
    • Xi‑Dong Li
  • View Affiliations / Copyright

    Affiliations: Department of Neurology and the Key Laboratory of Brain and Spine Injury, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Neurology, Fuxin Central Hospital, Fuxin, Liaoning 123000, P.R. China
  • Pages: 1942-1948
    |
    Published online on: July 21, 2014
       https://doi.org/10.3892/mmr.2014.2402
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Abstract

The p38 pathway, which is important in mitogen‑activated protein kinase (MAPK) family protein signaling, leads to mitochondrial dysfunction and activation of caspase‑3. B-cell lymphoma 2 (Bcl‑2) family members are involved in the regulation of activities associated with the survival and death of neurons through apoptosis and have important functions in most types of apoptosis. In the present study, the effects of the p38 MAPK inhibitor SB203580 on N‑methyl‑d‑aspartate (NMDA)‑induced cerebral cortical neuron apoptosis were observed to further analyze the possible mechanisms of NMDA‑induced neuronal death. Cultured primary cortical neurons were randomly divided into five groups: A control group, NMDA group and three SB203580 interventional groups. The lactate dehydrogenase (LDH) and MTT assays were employed to investigate the effects of the drugs on apoptosis. The morphology of apoptotic cells was observed using acridine orange/ethidium bromide (AO/EB) fluorescence staining. The expression levels of phospho‑(p)‑p38MAPK, Bcl‑2 and Bcl-2-associated X (Bax) were assessed by immunohistochemical methods and western blot analysis to investigate the possible underlying protective mechanisms. The cell viability markedly decreased following incubation with NMDA. The protein levels of cell death repressor Bcl‑2 and the levels of Bcl‑2/Bax were downregulated. The protein levels of p‑p38MAPK and cell death promoter Bax increased significantly in cells with NMDA treatment. However, these changes were inhibited by SB203580 treatment, particularly in the high‑dose group. Neuronal death induced by NMDA in primary cortical neurons was caused in part by apoptosis, which was mediated through the activation of the p38 signaling pathway by NMDA. SB203580 has neuroprotective effects against NMDA‑induced apoptosis.
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1 

Molz S, Decker H, Dal-Cim T, Cremonez C, Cordova FM, Leal RB and Tasca CI: Glutamate-induced toxicity in hippocampal slices involves apoptotic features and p38 MAPK signaling. Neurochem Res. 33:27–36. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Chen J, Errico SL and Freed WJ: Reactive oxygen species and p38 phosphorylation regulate the protective effect of Δ9-tetrahydrocannabinol in the apoptotic response to NMDA. Neurosci Lett. 389:99–103. 2005.

3 

Yang XR, Sun P, Qin HP, Si PP, Sun XF and Zhang C: Involvement of MAPK pathways in NMDA-induced apoptosis of rat cortical neurons. Sheng Li Xue Bao. 64:609–616. 2012.PubMed/NCBI

4 

Lu TH, Hsieh SY, Yen CC, et al: Involvement of oxidative stress-mediated ERK1/2 and p38 activation regulated mitochondria-dependent apoptotic signals in methylmercury-induced neuronal cell injury. Toxicol Lett. 204:71–80. 2011. View Article : Google Scholar

5 

Zhang R, Sun L, Hayashi Y, Liu X, Koyama S, Wu Z and Nakanishi H: Acute p38-mediated inhibition of NMDA-induced outward currents in hippocampal CA1 neurons by interleukin-1beta. Neurobiol Dis. 38:68–77. 2010. View Article : Google Scholar : PubMed/NCBI

6 

Dunleavy M, Provenzano G, Henshall DC and Bozzi Y: Kainic acid-induced seizures modulate Akt (SER473) phosphorylation in the hippocampus of dopamine D2 receptor knockout mice. J Mol Neurosci. 49:202–210. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Giordano G, Klintworth HM, Kavanagh TJ and Costa LG: Apoptosis induced by domoic acid in mouse cerebellar granule neurons involves activation of p38 and JNK MAP kinases. Neurochem Int. 52:1100–1105. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Ola MS, Nawaz M and Ahsan H: Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem. 351:41–58. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Neoh CA, Wang RY, Din ZH, et al: Induction of apoptosis by sinulariolide from soft coral through mitochondrial-related and p38MAPK pathways on human bladder carcinoma cells. Mar Drugs. 10:2893–2911. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Grethe S, Ares MP, Andersson T and Pörn-Ares MI: p38 MAPK mediates TNF-induced apoptosis in endothelial cells via phosphorylation and downregulation of Bcl-x(L). Exp Cell Res. 298:632–642. 2004. View Article : Google Scholar : PubMed/NCBI

11 

Liang HL, Dhar SS and Wong-Riley MT: p38 mitogen-activated protein kinase and calcium channels mediate signaling in depolarization-induced activation of peroxisome proliferator-activated receptor gamma coactivator-1alpha neurons. J Neurosci Res. 88:640–649. 2010.

12 

Yan Y, Bian JC, Zhong LX, Zhang Y, Sun Y and Liu ZP: Oxidative stress and apoptotic changes of rat cerebral cortical neurons exposed to cadmium in vitro. Biomed Environ Sci. 25:172–181. 2012.PubMed/NCBI

13 

Sanchez A, Tripathy D, Yin X, Luo J, Martinez J and Grammas P: Pigment epithelium-derived factor (PEDF) protects cortical neurons in vitro from oxidant injury by activation of extracellular signal-regulated kinase (ERK) 1/2 and induction of Bcl-2. Neurosci Res. 72:1–8. 2012. View Article : Google Scholar

14 

Guo RB, Wang GF, Zhao AP, Gu J, Sun XL and Hu G: Paeoniflorin protects against ischemia-induced brain damages in rats via inhibiting MAPKs/NF-kB-mediated inflammatory responses. PLoS One. 7:e497012012. View Article : Google Scholar : PubMed/NCBI

15 

Śmiałowska M, Gołembiowska K, Kajta M, Zieba B, Dziubina A and Domin H: Selective mGluR1 antagonist EMQMCM inhibits the kainate-induced excitotoxicity in primary neuronal cultures and in the rat hippocampus. Neurotox Res. 21:379–392. 2012.PubMed/NCBI

16 

Tiwari M, Lopez-Cruzan M, Morgan WW and Herman B: Loss of caspase-2-dependent apoptosis induces autophagy after mitochondrial oxidative stress in primary cultures of young adult cortical neurons. J Biol Chem. 286:8493–8506. 2011. View Article : Google Scholar

17 

Liu B, Zhang H, Xu C, et al: Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons. Brain Res. 1375:59–67. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Xu Z, Wang BR, Wang X, Kuang F, Duan XL, Jiao XY and Ju G: ERK 1/2 and p38 mitogen-activated protein kinase mediate iNOS-induced spinal neuron degeneration after acute traumatic spinal cord injury. Life Sci. 79:1895–1905. 2006. View Article : Google Scholar

19 

Jiang W, Van Cleemput J, Sheerin AH, et al: Involvement of extracellular regulated kinase and p38 kinase in hippocampal seizure tolerance. J Neurosci Res. 81:581–588. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Segura Torres JE, Chaparro-Huerta V, Rivera Cervantres MC, Montes-González R, Flores Soto ME and Beas-Zárate C: Neuronal cell death due to glutamate excitotocity is mediated by P38 activation in the rat cerebral cortex. Neurosci Lett. 403:233–238. 2006.PubMed/NCBI

21 

Miloso M, Scuteri A, Foudah D and Tredici G: MAPKs as mediators of cell fate determination: an approach to neurodegenerative diseases. Curr Med Chem. 15:538–548. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Chen S, Xu Y, Xu B, et al: CaMKII is involved in cadmium activation of MAPK and mTOR pathways leading to neuronal cell death. J Neurochem. 119:1108–1118. 2011. View Article : Google Scholar : PubMed/NCBI

23 

Zhang Y and Bhavnani BR: Glutamate-induced apoptosis in primary cortical neurons is inhibited by equine estrogens via down-regulation of caspase-3 and prevention of mitochondrial cytochrome c release. BMC Neurosci. 6:132005. View Article : Google Scholar

24 

Liu XW, Ma C, Xing RX, et al: The calmodulin-dependent protein kinase II inhibitor KN-93 protects rat cerebral cortical neurons from N-methyl-D-aspartic acid-induced injury. NRR. 8:111–120. 2013.PubMed/NCBI

25 

Xu B, Xu Z, Deng Y, Liu W, Yang H and Wei YG: MK-801 protects against intracellular Ca(2+) overloading and improves N-methyl-D-aspartate receptor expression in cerebral cortex of methylmercury-poisoned rats. J Mol Neurosci. 49:162–171. 2013.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu XW, Ji EF, He P, Xing RX, Tian BX and Li XD: Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons. Mol Med Rep 10: 1942-1948, 2014.
APA
Liu, X., Ji, E., He, P., Xing, R., Tian, B., & Li, X. (2014). Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons. Molecular Medicine Reports, 10, 1942-1948. https://doi.org/10.3892/mmr.2014.2402
MLA
Liu, X., Ji, E., He, P., Xing, R., Tian, B., Li, X."Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons". Molecular Medicine Reports 10.4 (2014): 1942-1948.
Chicago
Liu, X., Ji, E., He, P., Xing, R., Tian, B., Li, X."Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons". Molecular Medicine Reports 10, no. 4 (2014): 1942-1948. https://doi.org/10.3892/mmr.2014.2402
Copy and paste a formatted citation
x
Spandidos Publications style
Liu XW, Ji EF, He P, Xing RX, Tian BX and Li XD: Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons. Mol Med Rep 10: 1942-1948, 2014.
APA
Liu, X., Ji, E., He, P., Xing, R., Tian, B., & Li, X. (2014). Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons. Molecular Medicine Reports, 10, 1942-1948. https://doi.org/10.3892/mmr.2014.2402
MLA
Liu, X., Ji, E., He, P., Xing, R., Tian, B., Li, X."Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons". Molecular Medicine Reports 10.4 (2014): 1942-1948.
Chicago
Liu, X., Ji, E., He, P., Xing, R., Tian, B., Li, X."Protective effects of the p38 MAPK inhibitor SB203580 on NMDA‑induced injury in primary cerebral cortical neurons". Molecular Medicine Reports 10, no. 4 (2014): 1942-1948. https://doi.org/10.3892/mmr.2014.2402
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