1. Tetrahydroxy Stilbene Glucoside Promotes Mitophagy and Ameliorates Neuronal Injury after Cerebral Ischemia Reperfusion via Promoting USP10-Mediated YBX1 Stability.
- Author
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Li Y, Hu K, Li J, Yang X, Wu X, Liu Q, Chen Y, Ding Y, Liu L, Yang Q, and Wang G
- Subjects
- Animals, Male, Neuroprotective Agents pharmacology, Brain Ischemia metabolism, Brain Ischemia drug therapy, Infarction, Middle Cerebral Artery drug therapy, Rats, Ubiquitin-Protein Ligases metabolism, Ubiquitin-Protein Ligases genetics, Apoptosis drug effects, Apoptosis physiology, Protein Kinases metabolism, Disease Models, Animal, Ischemic Stroke drug therapy, Ischemic Stroke metabolism, Mitophagy drug effects, Mitophagy physiology, Rats, Sprague-Dawley, Reperfusion Injury metabolism, Reperfusion Injury drug therapy, Neurons drug effects, Neurons metabolism, Ubiquitin Thiolesterase metabolism, Glucosides pharmacology, Stilbenes pharmacology, Y-Box-Binding Protein 1 metabolism
- Abstract
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., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Li et al.)
- Published
- 2024
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