Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Ce
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40(4):699-707,2020
699
Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca2+-STIM1/Orai1 Signaling* Yi-da HU1, Chao-liang TANG2, Jia-zhen JIANG3, Hai-yan LV4, Yuan-bo WU5, Xiu-de QIN6, Si SHI1, Bo ZHAO1, Xiao-nan ZHU7, Zhong-yuan XIA1 1 Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, China 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 3 Department of Emergency, Huashan Hospital North, Fudan University, Shanghai 201907, China 4 Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 201620, China 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 6 Department of Neurology, Shenzhen Traditional Chinese Medicine Hospital, the Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen 518033, China 7 Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China Huazhong University of Science and Technology 2020
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 ischemiareperfusion injury. Key words: dexmedetomidine; neuroprotection; Ca2+; STIM1/Orai1; autophagy; PC12 cells; neuronal apoptosis
The PC12 cell line is derived from a pheochromocytoma of the rat adrenal medulla. It can acquire neuron-like properties when exposed to nerve growth factor
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