title: Ginkgolide B prevents cathepsin-mediated cell death following cerebral ischemia/reperfusion injury.
abstract: Ginkgolide B (GB) has been shown to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) injury. However, the underlying mechanism by which GB prevents ischemic cell death remains unclear. Lysosomal proteases, including cathepsins B and L, have been implicated in ischemic cell death following reperfusion. Therefore, in the present study, we investigated the role of GB with respect to cathepsin-mediated cell death following I/R. Both the expression and enzymatic activity of cathepsins B and L were significantly increased in the ischemic cortex following cerebral I/R injury. We found that GB treatment markedly decreased the activity and expression of cathepsins B and L following I/R. Moreover, GB reduced necrotic and apoptotic cell death following I/R. These data strongly suggest that GB prevents cathepsin-mediated cell death following focal cerebral I/R injury, and they might provide new insights into the mechanism of the neuroprotective effects of GB.
authors.affiliation: aDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai bDepartment of Neurosurgery, Affiliated Hospital of Nantong University cThe Second People's Hospital of Nantong, Nantong dDepartment of Emergency Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xuan-Feng
authors.initials: XF
authors.lastname: Qin
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Lu
authors.forename: Jian-Bin
authors.initials: JB
authors.lastname: Ge
authors.forename: Hong-Zhi
authors.initials: HZ
authors.lastname: Xu
authors.forename: Hai-Dong
authors.initials: HD
authors.lastname: Qin
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002401:Cathepsin B / Q000378:metabolism; D056668:Cathepsin L / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D015536:Down-Regulation / Q000187:drug effects; D046934:Ginkgolides / Q000627:therapeutic use*; D007783:Lactones / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009336:Necrosis / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index
chemical_list: D046934:Ginkgolides; D007783:Lactones; D018696:Neuroprotective Agents; C045856:ginkgolide B; D002403:Cathepsins; D002401:Cathepsin B; C533915:Ctsb protein, mouse; D056668:Cathepsin L; C534278:Ctsl protein, mouse