title: Protein tyrosine kinase regulates α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons.
abstract: This study was performed to investigate the modulation effect of protein tyrosine kinase on postsynaptic a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor trafficking induced by acute hypoxia in cultured brainstem neurons. The cultured neurons were exposed to 1% O2 and the expression of AMPA receptor subunit GluR2 on the cell surface was significantly increased, while total GluR2 was not markedly changed. Furthermore, the hypoxia-induced increase in GluR2 expression on the cell surface was partially blocked by the protein tyrosine kinase membrane-permeable inhibitor genistein. In contrast, both the protein tyrosine kinase agonist nerve growth factor and protein tyrosine phosphatase inhibitor vanadate promoted the hypoxia-induced increase of GluR2 expression on cell surface. Moreover, GluR2 could be phosphorylated by tyrosine under normoxia and hypoxia conditions in vitro on brainstem neurons, and tyrosine phosphorylation of GluR2 was significantly stronger under hypoxia conditions. Our results indicate that acute hypoxia induces the AMPA receptor subunit GluR2 to rapidly migrate to the cell membrane to modify the strength of the synapse. This study indicates that tyrosine phosphorylation of the receptor is an important pathway regulating the rapid migration of GluR2 in the postsynaptic domain induced by hypoxia.
authors.affiliation: Shandong Key Laboratory of Robotics and Intelligent Technology, Shandong University of Science and Technology, Qingdao, China.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Neurobiology, School of Life Science, Peaking University, Beijing, China.
authors.forename: L C
authors.initials: LC
authors.lastname: Yu
authors.affiliation: Department of Neurobiology & Anatomy, Drexel University College of Medicine, Philadelphia, PA, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Li
mesh_terms: D000818:Animals; D001933:Brain Stem / Q000166:cytology; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019833:Genistein / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D047428:Protein Kinase Inhibitors; D018091:Receptors, AMPA; D019833:Genistein; D011505:Protein-Tyrosine Kinases; C104722:glutamate receptor ionotropic, AMPA 2; D010100:Oxygen