Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis
Xanomeline, a muscarinic acetylcholine receptor agonist, is one of the first compounds that was found to be effective in the treatment of schizophrenics and attenuating behavioral disturbances of patients with Alzheimer’s disease (AD). However, its role in ischemia-induced injury due to oxygen and g...
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doaj-c97c06f7ace34aa38d41886889e7bcf42020-11-25T02:48:49ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-06-011110.3389/fphys.2020.00656534047Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and ApoptosisRujuan Xin0Rujuan Xin1Zhongjian Chen2Jin Fu3Fuming Shen4Quangang Zhu5Fang Huang6Department of Pharmacy, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, ChinaDepartment of Pharmacy, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacy, Ninghai First Hospital, Zhejiang, ChinaDepartment of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, ChinaDepartment of Pharmacy, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Pharmacy, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, ChinaXanomeline, a muscarinic acetylcholine receptor agonist, is one of the first compounds that was found to be effective in the treatment of schizophrenics and attenuating behavioral disturbances of patients with Alzheimer’s disease (AD). However, its role in ischemia-induced injury due to oxygen and glucose deprivation (OGD) remains unclear. Primary rat neuronal cells were exposed to OGD and treated with xanomeline. The effects of xanomeline on apoptosis, cell viability, lactate dehydrogenase (LDH) levels, and reactive oxygen species (ROS) were determined using an Annexin V Apoptosis Detection Kit, a non-radioactive cell counting kit-8 (CCK-8) assay, colorimetric LDH cytotoxicity assay kit, and a dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay, respectively, and the expressions of Sirtuin 1, haem oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2), poly ADP-ribose polymerase (PARP), and hypoxia-inducible factor α (HIF-1α) as well as the level of phosphorylated kinase B (p-Akt) were determined by Western blotting. Compared with the control, xanomeline pretreatment increased the viability of isolated cortical neurons and decreased the LDH release induced by OGD. Compared with OGD-treated cells, xanomeline inhibited apoptosis, reduced ROS production, attenuated the OGD-induced HIF-1α increase and partially reversed the reduction of HO-1, Sirtuin-1, Bcl-2, PARP, and p-Akt induced by OGD. In conclusion, xanomeline treatment protects cortical neuronal cells possibly through the inhibition of apoptosis after OGD.https://www.frontiersin.org/article/10.3389/fphys.2020.00656/fullxanomelineoxidative stressapoptosisoxygen and glucose deprivationcortical neurons |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rujuan Xin Rujuan Xin Zhongjian Chen Jin Fu Fuming Shen Quangang Zhu Fang Huang |
spellingShingle |
Rujuan Xin Rujuan Xin Zhongjian Chen Jin Fu Fuming Shen Quangang Zhu Fang Huang Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis Frontiers in Physiology xanomeline oxidative stress apoptosis oxygen and glucose deprivation cortical neurons |
author_facet |
Rujuan Xin Rujuan Xin Zhongjian Chen Jin Fu Fuming Shen Quangang Zhu Fang Huang |
author_sort |
Rujuan Xin |
title |
Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis |
title_short |
Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis |
title_full |
Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis |
title_fullStr |
Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis |
title_full_unstemmed |
Xanomeline Protects Cortical Cells From Oxygen-Glucose Deprivation via Inhibiting Oxidative Stress and Apoptosis |
title_sort |
xanomeline protects cortical cells from oxygen-glucose deprivation via inhibiting oxidative stress and apoptosis |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Physiology |
issn |
1664-042X |
publishDate |
2020-06-01 |
description |
Xanomeline, a muscarinic acetylcholine receptor agonist, is one of the first compounds that was found to be effective in the treatment of schizophrenics and attenuating behavioral disturbances of patients with Alzheimer’s disease (AD). However, its role in ischemia-induced injury due to oxygen and glucose deprivation (OGD) remains unclear. Primary rat neuronal cells were exposed to OGD and treated with xanomeline. The effects of xanomeline on apoptosis, cell viability, lactate dehydrogenase (LDH) levels, and reactive oxygen species (ROS) were determined using an Annexin V Apoptosis Detection Kit, a non-radioactive cell counting kit-8 (CCK-8) assay, colorimetric LDH cytotoxicity assay kit, and a dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay, respectively, and the expressions of Sirtuin 1, haem oxygenase-1 (HO-1), B-cell lymphoma 2 (Bcl-2), poly ADP-ribose polymerase (PARP), and hypoxia-inducible factor α (HIF-1α) as well as the level of phosphorylated kinase B (p-Akt) were determined by Western blotting. Compared with the control, xanomeline pretreatment increased the viability of isolated cortical neurons and decreased the LDH release induced by OGD. Compared with OGD-treated cells, xanomeline inhibited apoptosis, reduced ROS production, attenuated the OGD-induced HIF-1α increase and partially reversed the reduction of HO-1, Sirtuin-1, Bcl-2, PARP, and p-Akt induced by OGD. In conclusion, xanomeline treatment protects cortical neuronal cells possibly through the inhibition of apoptosis after OGD. |
topic |
xanomeline oxidative stress apoptosis oxygen and glucose deprivation cortical neurons |
url |
https://www.frontiersin.org/article/10.3389/fphys.2020.00656/full |
work_keys_str_mv |
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