title: Oxygen-glucose deprivation enhancement of cell death/apoptosis in PC12 cells and hippocampal neurons correlates with changes in neuronal excitatory amino acid neurotransmitter signaling and potassium currents.
abstract: Neuronal death is a pathophysiological process that is often caused by hypoxia/ischemia. However, the causes of hypoxia/ischemia-induced neuronal death are debated, and additional experimental data are needed to resolve this debate. In the present study, we applied oxygen-glucose deprivation (OGD) to PC12 cells and hippocampal neurons to establish a hypoxia/ischemia model. We evaluated the effects of OGD on cell death/apoptosis and on the levels of two excitatory amino acid neurotransmitters, aspartic acid and glutamic acid, in both hippocampal neurons and the medium used to culture the hippocampal neurons. We also evaluated GluR2 expression in hippocampal neurons as well as the effects of OGD on whole-cell potassium currents in PC12 cells and hippocampal neurons. Our experimental results showed that OGD significantly decreased cell viability and markedly enhanced apoptosis in PC12 cells and hippocampal neurons. OGD treatment for 3 h increased the levels of Asp and Glu in the medium used to culture hippocampal neurons, but decreased both the levels of Asp and Glu and GluR2 expression in hippocampal neurons. Furthermore, OGD altered the electrophysiological properties of voltage-dependent potassium channels in PC12 cells and hippocampal neurons in different ways; OGD decreased the voltage-dependent potassium current in PC12 cells, but increased this current in hippocampal neurons. On the basis of these results, we concluded that OGD enhanced neuronal cell death/apoptosis in addition to altering neuronal excitatory amino acid neurotransmitter signaling and whole-cell voltage-dependent potassium currents.
authors.affiliation: aDepartment of Zoology and Developmental Biology, College of Life Sciences, Nankai University, Tianjin, People's Republic of China bDepartment of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, New Brunswick, New Jersey, USA.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Ma
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: He
authors.forename: Kun
authors.initials: K
authors.lastname: Tian
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: An
authors.forename: Bin
authors.initials: B
authors.lastname: Heng
authors.forename: Lai-Hua
authors.initials: LH
authors.lastname: Xie
authors.forename: Yan-Qiang
authors.initials: YQ
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001224:Aspartic Acid / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D016716:PC12 Cells / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D024642:Potassium Channels, Voltage-Gated; D018091:Receptors, AMPA; D001224:Aspartic Acid; D018698:Glutamic Acid; C104722:glutamate receptor ionotropic, AMPA 2