Ying-Ying Wang1, Hao Zhang2, Tao Ma2, Yan Lu3, Hou-Yun Xie2, Wei Wang2, Yu-Heng Ma2, Guan-Hua Li2, Yong-Wang Li4. 1. Postgraduate Training Base of Jinzhou Medical University, The PLA Rocket Force Characteristic Medical Center, Beijing, 100088, PR China; Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, 100088, PR China. 2. Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, 100088, PR China. 3. Department of Neurology, The PLA Rocket Force Characteristic Medical Center, Beijing, 100088, PR China. 4. Department of Anesthesiology, The PLA Rocket Force Characteristic Medical Center, Beijing, 100088, PR China. Electronic address: liyongwangmed@163.com.
Abstract
OBJECTIVE: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca2+/calpain signaling. METHODS: Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca2+/calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca2+/calpain signaling participated in the neurotoxic effects of Piezo1 activation. RESULTS: Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746. CONCLUSION: Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca2+/calpain signaling.
OBJECTIVE: We investigated whether Piezo1 could regulate oxygen-glucose deprivation/reoxygenation injury of neurons through Ca2+/calpain signaling. METHODS:Piezo1 expression in rat brain cortex and PC12 cells were confirmed by immunohistochemistry, immunofluorescence and Western blotting. The effects of Yoda1 and GsMTx4 on OGD/R-induced decrease in cell viability, increase in cell apoptosis and activation of downstreaming Ca2+/calpain signaling were investigated. Furthermore, calpain signaling was inhibited by PD151746 to see whether Ca2+/calpain signaling participated in the neurotoxic effects of Piezo1 activation. RESULTS:Piezo1 expression was increased in rat cerebral cortex after ischemia/reperfusion and in PC12 cells after OGD/R. Activation of Piezo1 by Yoda1 enhanced OGD/R-induced cell viability inhibition, apoptosis, increase intracellular calcium levels and enhanced calpain activity while GsMTx4 showed the opposite effects. The effects of Piezo1 activation on cell viability and apoptosis were reversed by PD151746. CONCLUSION:Piezo1 could regulate neuron oxygen-glucose deprivation/reoxygenation injury via activation of Ca2+/calpain signaling.
Authors: Dongwon Choi; Eunkyung Park; Roy P Yu; Michael N Cooper; Il-Taeg Cho; Joshua Choi; James Yu; Luping Zhao; Ji-Eun Irene Yum; Jin Suh Yu; Brandon Nakashima; Sunju Lee; Young Jin Seong; Wan Jiao; Chester J Koh; Peter Baluk; Donald M McDonald; Sindhu Saraswathy; Jong Y Lee; Noo Li Jeon; Zhenqian Zhang; Alex S Huang; Bin Zhou; Alex K Wong; Young-Kwon Hong Journal: Circ Res Date: 2022-06-14 Impact factor: 23.213