γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress

Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing ne...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hui-qin Li, Sheng-nan Xia, Si-yi Xu, Pin-yi Liu, Yue Gu, Xin-yu Bao, Yun Xu, Xiang Cao
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/00a333b90dbd47daad4aac832e680f62
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:00a333b90dbd47daad4aac832e680f62
record_format	dspace
spelling	oai:doaj.org-article:00a333b90dbd47daad4aac832e680f622021-11-29T00:57:12Zγ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress1942-099410.1155/2021/2961079https://doaj.org/article/00a333b90dbd47daad4aac832e680f622021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/2961079https://doaj.org/toc/1942-0994Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ-glutamylcysteine (γ-GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ-GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ-GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ-GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ-GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ-GC may be a promising therapeutic agent for ischemic stroke.Hui-qin LiSheng-nan XiaSi-yi XuPin-yi LiuYue GuXin-yu BaoYun XuXiang CaoHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Hui-qin Li Sheng-nan Xia Si-yi Xu Pin-yi Liu Yue Gu Xin-yu Bao Yun Xu Xiang Cao γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress
description	Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ-glutamylcysteine (γ-GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ-GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ-GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ-GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1α (IRE1α) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ-GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ-GC may be a promising therapeutic agent for ischemic stroke.
format	article
author	Hui-qin Li Sheng-nan Xia Si-yi Xu Pin-yi Liu Yue Gu Xin-yu Bao Yun Xu Xiang Cao
author_facet	Hui-qin Li Sheng-nan Xia Si-yi Xu Pin-yi Liu Yue Gu Xin-yu Bao Yun Xu Xiang Cao
author_sort	Hui-qin Li
title	γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress
title_short	γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress
title_full	γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress
title_fullStr	γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress
title_full_unstemmed	γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress
title_sort	γ-glutamylcysteine alleviates ischemic stroke-induced neuronal apoptosis by inhibiting ros-mediated endoplasmic reticulum stress
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/00a333b90dbd47daad4aac832e680f62
work_keys_str_mv	AT huiqinli gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress AT shengnanxia gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress AT siyixu gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress AT pinyiliu gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress AT yuegu gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress AT xinyubao gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress AT yunxu gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress AT xiangcao gglutamylcysteinealleviatesischemicstrokeinducedneuronalapoptosisbyinhibitingrosmediatedendoplasmicreticulumstress
_version_	1718407626020093952

γ-Glutamylcysteine Alleviates Ischemic Stroke-Induced Neuronal Apoptosis by Inhibiting ROS-Mediated Endoplasmic Reticulum Stress

Ejemplares similares