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Remote Ischemic Postconditioning Alleviates Cerebral Ischemic Injury by Attenuating Endoplasmic Reticulum Stress-Mediated Apoptosis

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Abstract

Remote ischemic postconditioning (RIPostC) has been proved to protect the brain from stroke, but the precise mechanism remains not fully understood. In the present study, we aimed to investigate whether RIPostC attenuates cerebral ischemia-reperfusion injury by abating endoplasmic reticulum (ER) stress response. CHOP, a multifunctional transcription factor in ER stress, regulates the expression of genes related to apoptosis, such as Bim and Bcl-2. Male SD rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion, and RIPostC was induced by three cycles of 10 min ischemia and 10 min reperfusion on bilateral femoral arteries immediately after ischemia. CHOP siRNA (CHOPi) and control siRNA (Coni) were injected into the right lateral ventricle 30 min before the beginning of ischemia. RIPostC, CHOPi, or RIPostC + CHOPi application reduced infarct volume, improved the neurological function, and decreased cell apoptosis. RIPostC increased the protein level of glucose-regulated protein 78 (GRP78) and decreased the protein level of phosphorylated-EIF2α, caspase-12, and CHOP. Furthermore, the expression of CHOP, Bim and cleaved-caspase-3 was decreased, while Bcl-2 expression was increased in response to application of RIPostC, CHOPi, or RIPostC + CHOPi. In sum, RIPostC protects against ischemia-reperfusion brain injury in rats by attenuating ER stress response-induced apoptosis.

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Acknowledgments

This work was supported by the Natural Science Foundation of China (Grant nos. 81000504, 81171241, 81271462) and Beijing Natural Science Foundation (Grant nos. 7111003, 7132112).

Conflict of Interest

Xiangrong Liu, Shangfeng Zhao, Fang Liu, Jun Kang, Ao Xiao, Fang Li, Chencheng Zhang, Feng Yan, Haiping Zhao, Mei Luo, Yumin Luo, and Xunming Ji declare that they have no conflict of interest. All institutional and national guidelines for the care and use of laboratory animals were followed.

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Authors and Affiliations

  1. Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, People’s Republic of China

    Xiangrong Liu, Fang Liu, Ao Xiao, Fang Li, Chencheng Zhang, Feng Yan, Haiping Zhao, Mei Luo, Yumin Luo & Xunming Ji

  2. Key Laboratory of Neurodegenerative Diseases, Ministry of Education, Beijing, 100053, People’s Republic of China

    Xiangrong Liu, Fang Liu, Chencheng Zhang, Feng Yan, Haiping Zhao, Yumin Luo & Xunming Ji

  3. Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100073, People’s Republic of China

    Shangfeng Zhao & Jun Kang

  4. Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, People’s Republic of China

    Xunming Ji

  5. Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, China

    Xiangrong Liu, Fang Liu, Chencheng Zhang, Feng Yan, Haiping Zhao & Yumin Luo

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  1. Xiangrong Liu
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  2. Shangfeng Zhao
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  3. Fang Liu
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  9. Haiping Zhao
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  10. Mei Luo
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  11. Yumin Luo
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Correspondence to Yumin Luo or Xunming Ji.

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Liu, X., Zhao, S., Liu, F. et al. Remote Ischemic Postconditioning Alleviates Cerebral Ischemic Injury by Attenuating Endoplasmic Reticulum Stress-Mediated Apoptosis. Transl. Stroke Res. 5, 692–700 (2014). https://doi.org/10.1007/s12975-014-0359-5

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  • DOI: https://doi.org/10.1007/s12975-014-0359-5

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