PT  - JOURNAL ARTICLE
AU  - Li, Yuxian
AU  - Hu, Ke
AU  - Li, Jie
AU  - Yang, Xirong
AU  - Wu, Xiuyu
AU  - Liu, Qian
AU  - Chen, Yuefu
AU  - Ding, Yan
AU  - Liu, Lingli
AU  - Yang, Qiansheng
AU  - Wang, Guangwei
TI  - Tetrahydroxy Stilbene Glucoside Promotes Mitophagy and Ameliorates Neuronal Injury after Cerebral Ischemia Reperfusion via Promoting USP10-Mediated YBX1 Stability
AID  - 10.1523/ENEURO.0269-24.2024
DP  - 2024 Oct 01
TA  - eneuro
PG  - ENEURO.0269-24.2024
VI  - 11
IP  - 10
4099  - http://www.eneuro.org/content/11/10/ENEURO.0269-24.2024.short
4100  - http://www.eneuro.org/content/11/10/ENEURO.0269-24.2024.full
SO  - eNeuro2024 Oct 01; 11
AB  - Tetrahydroxy stilbene glucoside (TSG) from Polygonum multiflorum exerts neuroprotective effects after ischemic stroke. We explored whether TSG improved ischemic stroke injury via PTEN-induced kinase 1 (PINK1)/Parkin-mediated mitophagy. Oxygen glucose deprivation/reoxygenation (OGD/R) in vitro model and middle cerebral artery occlusion (MCAO) rat model were established. Cerebral injury was assessed by neurological score, hematoxylin and eosin staining, 2,3,5-triphenyltetrazolium chloride staining, and brain water content. Apoptosis, cell viability, and mitochondrial membrane potential were assessed by flow cytometry, cell counting kit-8, and JC-1 staining, respectively. Colocalization of LC3-labeled autophagosomes with lysosome-associated membrane glycoprotein 2-labeled lysosomes or translocase of outer mitochondrial membrane 20-labeled mitochondria was observed with fluorescence microscopy. The ubiquitination level was determined using ubiquitination assay. The interaction between molecules was validated by coimmunoprecipitation and glutathione S-transferase pull-down. We found that TSG promoted mitophagy and improved cerebral ischemia/reperfusion damage in MCAO rats. In OGD/R-subjected neurons, TSG promoted mitophagy, repressed neuronal apoptosis, upregulated Y-box binding protein-1 (YBX1), and activated PINK1/Parkin signaling. TSG upregulated ubiquitin-specific peptidase 10 (USP10) to elevate YBX1 protein. Furthermore, USP10 inhibited ubiquitination-dependent YBX1 degradation. USP10 overexpression activated PINK1/Parkin signaling and promoted mitophagy, which were reversed by YBX1 knockdown. Moreover, TSG upregulated USP10 to promote mitophagy and inhibited neuronal apoptosis. Collectively, TSG facilitated PINK1/Parkin pathway-mediated mitophagy by upregulating USP10/YBX1 axis to ameliorate ischemic stroke.