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Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca2+-STIM1/Orai1 Signaling

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Summary

Dexmedetomidine (DEX), a potent and highly selective agonist for α2-adrenergic receptors (α2AR), exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca2+ influx. However, the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation (OGD/R) injury in vitro are unknown. We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells, as evidenced by decreased oxidative stress, autophagy, and neuronal apoptosis. Specifically, DEX pretreatment decreased the expression levels of stromal interaction molecule 1 (STIM1) and calcium release-activated calcium channel protein 1 (Orai1), and reduced the concentration of intracellular calcium pools. In addition, variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions, which were modulated through STIM1/Orai1 signaling. Moreover, DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3 (LC3), hallmark markers of autophagy, and the formation of autophagosomes. In conclusion, these results suggested that DEX exerts neuroprotective effects against oxidative stress, autophagy, and neuronal apoptosis after OGD/R injury via modulation of Ca2+-STIM1/Orai1 signaling. Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.

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Acknowledgement

The authors are grateful for the enthusiastic support of Mr. Kai Zhang’s contribution to design the graphics.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Yi-da Hu, Si Shi, Bo Zhao & Zhong-yuan Xia

  2. Department of Anesthesiology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China

    Chao-liang Tang

  3. Department of Emergency, Huashan Hospital North, Fudan University, Shanghai, 201907, China

    Jia-zhen Jiang

  4. Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, 201620, China

    Hai-yan Lv

  5. Department of Neurology, the First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, China

    Yuan-bo Wu

  6. Department of Neurology, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, 518033, China

    Xiu-de Qin

  7. Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, 430060, China

    Xiao-nan Zhu

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  1. Yi-da Hu
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Correspondence to Zhong-yuan Xia.

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The authors declare that there is no conflict of interest regarding the publication of this article.

Additional information

This study was supported by grants from the National Natural Science Foundation of China (No. 81801175 and No. 81970722), the Fundamental Research Funds for the Central Universities (No. WK9110000044 and No. WK9110000036), China Scholarship Council (No. 201706270155), the China Postdoctoral Science Foundation (No. 2019M662179), and the Anhui Province Postdoctoral Science Foundation (No. 2019B324).

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Hu, Yd., Tang, Cl., Jiang, Jz. et al. Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca2+-STIM1/Orai1 Signaling. CURR MED SCI 40, 699–707 (2020). https://doi.org/10.1007/s11596-020-2201-5

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  • DOI: https://doi.org/10.1007/s11596-020-2201-5

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