title: P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration.
abstract: Recruitment of oligodendrocyte precursor cells (OPCs) to the lesions is the most important event for remyelination after central nervous system (CNS) injury or in demyelinating diseases. However, the underlying molecular mechanism is not fully understood. In the present study, we found high concentrations of ATP could increase the number of migrating OPCs in vitro, while after pretreatment with oxidized ATP (a P2X7 receptor antagonist), the promotive effect was attenuated. The promotive effect of 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'-triphosphate (BzATP) (a P2X7 receptor agonist) was more potent than ATP. After incubation with BzATP, the activity of Fyn, one member of the Src family of kinases, was enhanced. Moreover, the interaction between P2X7 and Fyn was identified by co-immunoprecipitation. After blocking the activity of Fyn or down-regulating the expression of Fyn, the migration of OPCs induced by BzATP was inhibited. These data indicate that P2X7 receptors/Fyn may mediate ATP-induced OPC migration under pathological conditions.
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Feng
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Gao
authors.forename: Ying-Yan
authors.initials: YY
authors.lastname: Pu
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Burnstock
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Xiang
authors.forename: Cheng
authors.initials: C
authors.lastname: He
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002469:Cell Separation; D006801:Humans; D016086:Lentivirus / Q000254:growth & development; D009836:Oligodendroglia / Q000187:drug effects*; D051076:Proto-Oncogene Proteins c-fyn / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
chemical_list: D058486:Receptors, Purinergic P2X7; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; C494961:Fyn protein, rat; D051076:Proto-Oncogene Proteins c-fyn