title: Propofol Prevents Hippocampal Neuronal Loss and Memory Impairment in Cerebral Ischemia Injury Through Promoting PTEN Degradation.
abstract: Neuroprotective effect of propofol against cerebral ischemia injury was widely investigated. However, its mechanisms remain unclear. Phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is supposed as a cell survival pathway, and phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a negative regulator of AKT phosphorylation. Whether PTEN was involved in the protective effect of propofol against cerebral ischemia injury was not elucidated. In this study, the function of PTEN in the acute phase of cerebral ischemia injury was investigated. Our data showed that propofol promoted the PTEN degradation in the acute phase of cerebral ischemia injury and concurrently activated AKT phosphorylation. The increase of ubiquitinated PTEN caused by cerebral ischemia injury were degraded in propofol-pretreated rats. Moreover, we evidenced that proteasome activity was stimulated in propofol-treated rats. These data pointed that PTEN degradation was facilitated in the acute phase after propofol treatment possibly through activating ubiquitin-proteasome system. Therefore, we applied PTEN inhibitor-bpV before cerebral ischemia injury. Like propofol, bpV pretreatment also mitigated cerebral ischemia injury-induced cell loss in CA1 region and memory impairment. Taken together, our data suggest that PTEN degradation is neuroprotective against cerebral ischemia injury and propofol facilitates PTEN degradation to prevent hippocampal neuronal loss and memory deficit in cerebral ischemia injury.
authors.affiliation: Department of Anesthesiology, Huai'an First Hospital, Nanjing Medical University, Nanjing, 223000, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Huai'an First Hospital, Nanjing Medical University, Nanjing, 223000, China.
authors.forename: Ye-Mu
authors.initials: YM
authors.lastname: Du
authors.affiliation: Department of Anesthesiology, Huai'an First Hospital, Nanjing Medical University, Nanjing, 223000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Huai'an First Hospital, Nanjing Medical University, Nanjing, 223000, China.
authors.forename: Dai
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Huai'an First Hospital, Nanjing Medical University, Nanjing, 223000, China. wangyuanlinwyl@sina.com.
authors.forename: Yuan-Lin
authors.initials: YL
authors.lastname: Wang
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy*; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D015742:Propofol / Q000494:pharmacology* / Q000627:therapeutic use; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D018696:Neuroprotective Agents; D051059:PTEN Phosphohydrolase; D046988:Proteasome Endopeptidase Complex; D015742:Propofol
keywords: Memory deficit; PTEN; Propofol; Ubiquitin-proteasome system