Geraniol-Mediated Suppression of Endoplasmic Reticulum Stress Protects against Cerebral Ischemia-Reperfusion Injury via the PERK-ATF4-CHOP Pathway

作者全名："Wu, Yu; Fan, Xiaomei; Chen, Sha; Deng, Ling; Jiang, Lu; Yang, Shaonan; Dong, Zhi"

作者地址："[Wu, Yu; Fan, Xiaomei; Chen, Sha; Deng, Ling; Jiang, Lu; Yang, Shaonan; Dong, Zhi] Chongqing Med Univ, Coll Pharmacol, Key Lab Biochem & Mol Pharmacol, Chongqing 400010, Peoples R China"

通信作者："Dong, Z (通讯作者)，Chongqing Med Univ, Coll Pharmacol, Key Lab Biochem & Mol Pharmacol, Chongqing 400010, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000908732300001

JCR分区：Q2

影响因子：5.6

年份：2023

卷号：24

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：cerebral ischemia-reperfusion injury (CIRI); geraniol; endoplasmic reticulum (ER) stress; apoptosis

摘要："Endoplasmic reticulum (ER) stress plays an important role in cerebral ischemia-reperfusion injury (CIRI). Geraniol has antioxidant, antibacterial, and anti-inflammatory activities. Studies have shown that geraniol has a protective effect against CIRI in rats, but the exact mechanism is unclear. Purpose: The aim of this study was to investigate the protective mechanism of geraniol against CIRI. We established a middle cerebral artery occlusion reperfusion model in rats and a PC12 cell oxygen-glucose deprivation/reoxygenation (OGD/R) model to observe the neuroprotective effects of geraniol. Neurological scoring, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin and eosin staining were used to evaluate the neuroprotective effects of geraniol against CIRI. ER-stress-related and apoptosis-related protein expression was detected via Western blotting and immunofluorescence. Apoptosis was also detected via TUNEL assays and flow cytometry. The fluorescent detection of intracellular calcium was achieved using fluorescent calcium-binding dyes, and transmission electron microscopy was used to assess the neuronal ultrastructure. Geraniol effectively attenuated cerebral infarction and pathological injury after CIRI, had a protective effect against CIRI, significantly reduced the expression of the ER-stress-related proteins P-PERK, ATF4, CHOP, and GRP78 and the pro-apoptotic protein BAX, increased the expression of the anti-apoptotic protein BCL-2, and reduced the occurrence of apoptosis. In the OGD/R model in PC12 cells, the protective effect of geraniol was the same as that in vivo. Our results suggest that geraniol has a protective effect against ischemic stroke by a mechanism possibly related to ER stress via the PERK-ATF4-CHOP pathway."

基金机构：Chongqing Yuzhong District Science Technology Commission of China; Outstanding Researcher Fund of the College of Pharmacology of Chongqing Medical University; [20210121]; [YXY2021BSH02]

基金资助正文：This work was supported by the Chongqing Yuzhong District Science Technology Commission of China (Grant Number: 20210121) and the Outstanding Researcher Fund of the College of Pharmacology of Chongqing Medical University (No. YXY2021BSH02).