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Article Open Access

Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo

  • Authors:
    • Xiaofeng Lei
    • Lijian Lei
    • Zhiqing Zhang
    • Yan Cheng
  • View Affiliations / Copyright

    Affiliations: Department of Neurology Medicine, Tianjin 4th Center Hospital, Tianjin, Hebei 300052, P.R. China, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China, Department of Neurology Medicine, Tianjin Medical University General Hospital, Tianjin, Hebei 300052, P.R. China
    Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 8039-8046
    |
    Published online on: April 24, 2018
       https://doi.org/10.3892/mmr.2018.8925
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Abstract

Neuroprotective strategies using diazoxide (DZX) have been demonstrated to limit ischemia/reperfusion (I/R)‑induced injury and cell apoptosis. In type 2 diabetes mellitus, DZX has been reported to improve β‑cell function and reduce their apoptosis, through suppressing endoplasmic reticulum (ER) stress. However, the effects of DZX on ER stress during I/R‑induced neuronal apoptosis in the hippocampus remains to be elucidated. In the present study, pretreatment of hippocampal neurons with DZX was revealed to inhibit oxygen‑glucose deprivation (OGD)‑stimulated apoptosis in vitro and to alleviate I/R‑induced hippocampal injury and behavioral deficits in rats in vivo. Furthermore, OGD and I/R were demonstrated to induce ER stress via upregulating the expression of ER stress‑associated proteins, including C/EBP homologous protein, 78 kDa glucose‑regulated protein and caspase‑12, whereas the exogenous administration of DZX effectively downregulated ER stress‑associated protein expression following OGD and I/R. In addition, DZX was revealed to significantly increase the protein expression of B‑cell lymphoma (Bcl)‑2 and suppress the expression of caspase‑3 and Bcl‑2‑associated X protein. These findings suggested that DZX may protect cells against apoptosis via regulating the expression of ER stress‑associated proteins in vitro and in vivo, thus enhancing the survival of hippocampal cells. The present results suggested a novel mechanism that may underlie the protective effect of DZX administration in the central nervous system.
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Copy and paste a formatted citation
Spandidos Publications style
Lei X, Lei L, Zhang Z and Cheng Y: Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo. Mol Med Rep 17: 8039-8046, 2018.
APA
Lei, X., Lei, L., Zhang, Z., & Cheng, Y. (2018). Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo. Molecular Medicine Reports, 17, 8039-8046. https://doi.org/10.3892/mmr.2018.8925
MLA
Lei, X., Lei, L., Zhang, Z., Cheng, Y."Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo". Molecular Medicine Reports 17.6 (2018): 8039-8046.
Chicago
Lei, X., Lei, L., Zhang, Z., Cheng, Y."Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo". Molecular Medicine Reports 17, no. 6 (2018): 8039-8046. https://doi.org/10.3892/mmr.2018.8925
Copy and paste a formatted citation
x
Spandidos Publications style
Lei X, Lei L, Zhang Z and Cheng Y: Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo. Mol Med Rep 17: 8039-8046, 2018.
APA
Lei, X., Lei, L., Zhang, Z., & Cheng, Y. (2018). Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo. Molecular Medicine Reports, 17, 8039-8046. https://doi.org/10.3892/mmr.2018.8925
MLA
Lei, X., Lei, L., Zhang, Z., Cheng, Y."Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo". Molecular Medicine Reports 17.6 (2018): 8039-8046.
Chicago
Lei, X., Lei, L., Zhang, Z., Cheng, Y."Diazoxide inhibits of ER stress‑mediated apoptosis during oxygen‑glucose deprivation in vitro and cerebral ischemia‑reperfusion in vivo". Molecular Medicine Reports 17, no. 6 (2018): 8039-8046. https://doi.org/10.3892/mmr.2018.8925
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