title: XAV939, a small molecular inhibitor, provides neuroprotective effects on oligodentrocytes.
abstract: White matter tracts are composed of axons and myelinating oligodendrocytes. Oligodendrocytes are the myelinating cells in the central nervous system that allow formation of myelin and saltatory nerve conduction. Cerebral white matter is highly vulnerable to ischemic injury in adults and neonates. White matter injury in newborn brains results in cerebral palsy and cognitive disability. In this study, we found that XAV939, a small-molecular inhibitor that stimulated β-catenin degradation by stabilizing axin, protected against serum and glucose deprivation (SGD)-induced cell death in oligodentrocyte cell line OLN-93 cells in a concentration-dependent manner. We further showed that XAV939 reduced caspase-3 and caspase-8 levels and increased the expression of phosphorylated Akt in SGD-induced OLN-93 cells. Our data demonstrate that XAV939 protects against neonatal hypoxic/ischemic injury. In summary, our results demonstrate that XAV939 confers neuroprotection against SGD-induced injury in OLN-93 cells via its antiapoptotic activity and the loss of oligodendrocytes and neurons in neonatal hypoxic/ischemic injury.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou City, China; The Institute of Neuroscience, Soochow University, Suzhou City, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Jizhen
authors.initials: J
authors.lastname: Li
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Miao
authors.forename: Xingshun
authors.initials: X
authors.lastname: Xu
authors.forename: Chun-Feng
authors.initials: CF
authors.lastname: Liu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009836:Oligodendroglia / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044967:Serum / Q000378:metabolism; D013997:Time Factors; D051176:beta Catenin / Q000378:metabolism
chemical_list: D002867:Chromones; D004791:Enzyme Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D009025:Morpholines; D018696:Neuroprotective Agents; C544261:XAV939; D051176:beta Catenin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D020169:Caspases
keywords: OLN-93; XAV939; apoptosis; oligodendrocytes; white matter injury