title: Neuroprotection by Carbenoxolone Against Ischemia Injury Involves PI3K/Akt Pathway.
abstract: BACKGROUND
  Previous experimental studies have shown some protective effects on brain ischemic injures in vivo and in vitro models. However, cotreatment with carbenoxolone (Cbx) and phosatidylinositol 3-kinase (PI3K) inhibitor LY 294002 to a focal cerebral ischemia and reperfusion rat model has not been studied yet. Here we investigate their protective effects on neural cells and examine the function of PI3K/Akt pathway in this protection.
  
  
  METHODS
  Both flow cytometry and western blot were used quantitatively and qualitatively to determine cell apoptosis.
  
  
  RESULTS
  The neural cell apoptosis is related with Cx43, and Bcl-2/Bax and caspase 3 pathways. The percentage of apoptosis cells following transient middle cerebral artery occlusion (MCAO) in mice decrease with the treatment of Cbx. Our data demonstrated that treatment with Cbx reduced cerebral injury in rats exposed to transient focal ischemia and reperfusion (I/R), and this was mediated by the activation of the PI3K/Akt pathways as well as by blocking the caspase 3 apoptosis pathway. LY294002 blocked the increase in phospho-AKT evoked by Cbx and abolished the associated protective effect.
  
  
  CONCLUSIONS
  Taken together, these findings provide evidence that Cbx protects neurons against ischemia injury and this neuroprotective effect involves the PI3K/Akt pathway.
authors.forename: Yu Kai
authors.initials: YK
authors.lastname: Wang
authors.forename: Fang
authors.initials: F
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Miao
authors.forename: HongYan
authors.initials: H
authors.lastname: Xie
authors.forename: Jia Chun
authors.initials: JC
authors.lastname: Feng
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000517:prevention & control*; D002229:Carbenoxolone / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002867:Chromones / Q000737:chemistry; D018031:Connexin 43 / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D020244:Infarction, Middle Cerebral Artery; D008297:Male; D009025:Morpholines / Q000737:chemistry; D000066829:Neuroprotection; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D002867:Chromones; D018031:Connexin 43; D004791:Enzyme Inhibitors; D009025:Morpholines; D018696:Neuroprotective Agents; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D002229:Carbenoxolone