title: Remote ischemic postconditioning alleviates cerebral ischemic injury by attenuating endoplasmic reticulum stress-mediated apoptosis.
abstract: Remote ischemic postconditioning (RIPostC) has been proved to protect the brain from stroke, but the precise mechanism remains not fully understood. In the present study, we aimed to investigate whether RIPostC attenuates cerebral ischemia-reperfusion injury by abating endoplasmic reticulum (ER) stress response. CHOP, a multifunctional transcription factor in ER stress, regulates the expression of genes related to apoptosis, such as Bim and Bcl-2. Male SD rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion, and RIPostC was induced by three cycles of 10 min ischemia and 10 min reperfusion on bilateral femoral arteries immediately after ischemia. CHOP siRNA (CHOPi) and control siRNA (Coni) were injected into the right lateral ventricle 30 min before the beginning of ischemia. RIPostC, CHOPi, or RIPostC + CHOPi application reduced infarct volume, improved the neurological function, and decreased cell apoptosis. RIPostC increased the protein level of glucose-regulated protein 78 (GRP78) and decreased the protein level of phosphorylated-EIF2α, caspase-12, and CHOP. Furthermore, the expression of CHOP, Bim and cleaved-caspase-3 was decreased, while Bcl-2 expression was increased in response to application of RIPostC, CHOPi, or RIPostC + CHOPi. In sum, RIPostC protects against ischemia-reperfusion brain injury in rats by attenuating ER stress response-induced apoptosis.
authors.affiliation: Cerebrovascular Diseases Research Institute, Xuanwu Hospital of Capital Medical University, 45 Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Liu
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Zhao
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.forename: Ao
authors.initials: A
authors.lastname: Xiao
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Chencheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Yan
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhao
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.forename: Yumin
authors.initials: Y
authors.lastname: Luo
authors.forename: Xunming
authors.initials: X
authors.lastname: Ji
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000628:therapy*; D019194:Ischemic Preconditioning; D008297:Male; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000628:therapy; D020521:Stroke / Q000378:metabolism / Q000628:therapy*; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: C497251:Ddit3 protein, rat; D034741:RNA, Small Interfering; D051742:Transcription Factor CHOP