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Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis

  • Authors:
    • Dandan Xu
    • Tingting Kong
    • Baohua Cheng
    • Rumin Zhang
    • Chunqing Yang
    • Jing Chen
    • Chunmei Wang
  • View Affiliations / Copyright

    Affiliations: Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250014, P.R. China, Neurobiology Key Laboratory of Jining Medical University in Colleges of Shandong, Jining, Shandong 272067, P.R. China
    Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 266
    |
    Published online on: February 8, 2021
       https://doi.org/10.3892/mmr.2021.11905
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Abstract

Orexin‑A (OXA) protects neurons against cerebral ischemia‑reperfusion injury (CIRI). Endoplasmic reticulum stress (ERS) induces apoptosis after CIRI by activating caspase‑12 and the CHOP pathway. The present study aimed to determine whether OXA mitigates CIRI by inhibiting ERS‑induced neuronal apoptosis. A model of CIRI was established, in which rats were subjected to middle cerebral artery occlusion with ischemic intervention for 2 h, followed by reperfusion for 24 h. Neurological deficit examination and 2,3,5‑triphenyltetrazolium chloride staining were performed to assess the level of CIRI and neuroprotection by OXA. Expression levels of ERS‑related proteins and cleaved caspase‑3 were measured via western blotting, while the rate of neuronal apoptosis in the cortex was determined using a TUNEL assay. OXA treatment decreased the infarct volume of rats after CIRI and attenuated neuron apoptosis. Furthermore, administration of OXA decreased the expression levels of GRP78, phosphorylated (p)‑PERK, p‑eukaryotic initiation factor‑2α, p‑inositol requiring enzyme 1α, p‑JNK, cleaved caspase‑12, CHOP and cleaved caspase‑3, all of which were induced by CIRI. Collectively, these findings suggested that OXA attenuated CIRI by inhibiting ERS‑mediated apoptosis, thus clarifying the mechanism underlying its neuroprotective effect and providing a novel therapeutic direction for the treatment of CIRI.
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Copy and paste a formatted citation
Spandidos Publications style
Xu D, Kong T, Cheng B, Zhang R, Yang C, Chen J and Wang C: Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis. Mol Med Rep 23: 266, 2021.
APA
Xu, D., Kong, T., Cheng, B., Zhang, R., Yang, C., Chen, J., & Wang, C. (2021). Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis. Molecular Medicine Reports, 23, 266. https://doi.org/10.3892/mmr.2021.11905
MLA
Xu, D., Kong, T., Cheng, B., Zhang, R., Yang, C., Chen, J., Wang, C."Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 23.4 (2021): 266.
Chicago
Xu, D., Kong, T., Cheng, B., Zhang, R., Yang, C., Chen, J., Wang, C."Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 23, no. 4 (2021): 266. https://doi.org/10.3892/mmr.2021.11905
Copy and paste a formatted citation
x
Spandidos Publications style
Xu D, Kong T, Cheng B, Zhang R, Yang C, Chen J and Wang C: Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis. Mol Med Rep 23: 266, 2021.
APA
Xu, D., Kong, T., Cheng, B., Zhang, R., Yang, C., Chen, J., & Wang, C. (2021). Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis. Molecular Medicine Reports, 23, 266. https://doi.org/10.3892/mmr.2021.11905
MLA
Xu, D., Kong, T., Cheng, B., Zhang, R., Yang, C., Chen, J., Wang, C."Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 23.4 (2021): 266.
Chicago
Xu, D., Kong, T., Cheng, B., Zhang, R., Yang, C., Chen, J., Wang, C."Orexin-A alleviates cerebral ischemia-reperfusion injury by inhibiting endoplasmic reticulum stress-mediated apoptosis". Molecular Medicine Reports 23, no. 4 (2021): 266. https://doi.org/10.3892/mmr.2021.11905
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