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BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis.
Liu, Xia; Ye, Qinlian; Huang, Zhengzheng; Li, Xiuping; Zhang, Liping; Liu, Xuan; Wu, Yun-Cheng; Brockmeier, Ulf; Hermann, Dirk M; Wang, Ya-Chao; Ren, Lijie.
Afiliação
  • Liu X; Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, China.
  • Ye Q; Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China (Xia Liu, Y.-C.W.).
  • Huang Z; Department of Neurosurgery, The Institute Translational Medicine (Q.Y., Y.-C.W.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, China.
  • Li X; Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, China.
  • Zhang L; Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, China.
  • Liu X; Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, China.
  • Wu YC; Department of Neurology (Xia Liu, Z.H., X. Li, L.Z., Xuan Liu, L.R.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, China.
  • Brockmeier U; Department of Neurosurgery, The Institute Translational Medicine (Q.Y., Y.-C.W.), The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, China.
  • Hermann DM; Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China (Xia Liu, Y.-C.W.).
  • Wang YC; Department of Neurology, University Hospital Essen, Germany (U.B., D.M.H.).
  • Ren L; Department of Neurology, University Hospital Essen, Germany (U.B., D.M.H.).
Stroke ; 54(8): 2114-2125, 2023 08.
Article em En | MEDLINE | ID: mdl-37377010
BACKGROUND: The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke. METHODS: Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin & Eosin staining were performed to evaluate cerebral injury following MCAO/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation/reoxygenation-induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis. RESULTS: The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro. CONCLUSIONS: Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia/reperfusion and hypoxia/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Isquemia Encefálica / AVC Isquêmico Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Traumatismo por Reperfusão / Isquemia Encefálica / AVC Isquêmico Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article