P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration |
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Authors: | Ji-Feng Feng Xiao-Fei Gao Ying-yan Pu Geoffrey Burnstock Zhenghua Xiang Cheng He |
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Affiliation: | 1.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 ;2.Autonomic Neuroscience Centre, University College Medical School, Royal Free Campus, Rowland Hill Street, London, NW3 2PF UK ;3.Department of Pharmacology and Therapeutics, The University of Melbourne, Melbourne, Australia |
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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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11302-015-9458-3) contains supplementary material, which is available to authorized users. |
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Keywords: | P2X7 receptors Src family kinase Fyn kinase Migration OPCs ATP |
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