Facilitating Mitophagy via Pink1/Parkin2 Signaling Is Essential for the Neuroprotective Effect of beta-Caryophyllene against CIR-Induced Neuronal Injury

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

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

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

来源：BRAIN SCIENCES

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000833360900001

JCR分区：Q3

影响因子：3.3

年份：2022

卷号：12

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：mitophagy; beta-caryophyllene; cerebral ischemia-reperfusion; Pink1/Parkin2 pathway; neuronal injury

摘要："Mitophagy is an important mechanism for maintaining mitochondrial homeostasis through elimination of damaged or dysfunctional mitochondria following cerebral ischemia-reperfusion (CIR) injury. beta-Caryophyllene (BCP) is a natural sesquiterpene compound found in the essential oil of plants and has been shown to ameliorate CIR injury. However, whether BCP protects neurons from CIR injury by activating mitophagy is still unclear, and the underlying mechanism remains unknown. In the present study, a mouse neuron HT-22 cell of oxygen-glucose deprivation/reoxygenation (OGD/R) and C57BL/6 male mouse of transient middle artery occlusion followed by 24 h reperfusion (MCAO/R) were established the model of CIR injury. Our results show that BCP remarkably protected against cell death and apoptosis induced by OGD/R, and decreased neurologic injury, infarct volume, and the injury of neurons in CA1 region on MCAO/R mice. In addition, BCP accelerated mitophagy by regulating expression of mitochondrial autophagy marker molecules and the mt-Atp6/Rpl13 ratio (reflecting the relative number of mitochondria), and promoting autophagosome formation compared with OGD/R and MCAO/R groups both in vitro and in vivo. Furthermore, this study revealed that BCP pre-treatment could activate the Pink1/Parkin2 signaling pathway, also with mitophagy activation. To explore the mechanisms, mitochondrial division inhibitor-1 (Mdivi-1) was used to investigate the role of BCP in CIR injury. We found that Mdivi-1 not only decreased BCP-induced facilitation of mitophagy, but also significantly weakened BCP-induced protection against OGD/R and MCAO/R models, which was consistent with levels of Pink1/Parkin2 signaling pathway. Taken together, these results suggest that facilitating mitophagy via Pink1/Parkin2 signaling is essential for the neuroprotective effect of BCP against CIR injury."

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

基金资助正文："This research was funded by 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, grant number YXY2021BSH02."