title: Prevention of cell death by the zinc ion chelating agent TPEN in cultured PC12 cells exposed to Oxygen-Glucose Deprivation (OGD).
abstract: To elucidate the role of Zn(2+)-associated glutamate signaling pathway and voltage-dependent outward potassium ion currents in neuronal death induced by hypoxia-ischemia, PC12 cells were exposed to Oxygen-Glucose Deprivation (OGD) solution mimicking the hypoxic-ischemic condition in neuron, and the effect of N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a specific Zn(2+) chelating agent on OGD-induced neuronal death was assessed in the present study. The cell survival rate, apoptosis status, potassium channel currents, intracellular free glutamate concentration and GluR2 expression in PC12 cells exposed to OGD in the absence or presence of TPEN for different time were investigated. The results showed that OGD exposure increased apoptosis, reduced the cell viability (P < 0.01 at 3h, 6h and 24h, respectively compared to control), changed the voltage-dependent outward potassium ion current (increase at 1h, but decrease at 3h) and decreased the concentration of intracellular glutamate (P < 0.05 at 3h and 6h, P < 0.01 at 24h respectively compared to control) and GluR2 expression (P < 0.05 at 3h, 6h and 24h, respectively compared to control) in PC12 cells. TPEN partially reversed the influence resulted from OGD. These results suggest that OGD-induced cell apoptosis and/or death is mediated by the alteration in glutamate signaling pathway and the voltage-dependent outward potassium ion currents, while TPEN effectively prevent cell apoptosis and/or death under hypoxic-ischemic condition.
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yue-yang
authors.initials: YY
authors.lastname: Huang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Yu-xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Hong-gang
authors.initials: HG
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Deng
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Heng
authors.affiliation: Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Rutgers, The State University of New Jersey, USA.
authors.forename: Lai-hua
authors.initials: LH
authors.lastname: Xie
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, PR China. Electronic address: liuyanq@nankai.edu.cn.
authors.forename: Yan-qiang
authors.initials: YQ
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D005029:Ethylenediamines / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D016716:PC12 Cells / Q000187:drug effects; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D002614:Chelating Agents; D005029:Ethylenediamines; D024642:Potassium Channels, Voltage-Gated; D018091:Receptors, AMPA; D018698:Glutamic Acid; D005947:Glucose; D015032:Zinc; C104722:glutamate receptor ionotropic, AMPA 2; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D010100:Oxygen
keywords: Hypoxic–ischemic condition; Neuronal death; PC12 cells; TPEN; Zn(2+)