title: Genistein inhibition of OGD-induced brain neuron death correlates with its modulation of apoptosis, voltage-gated potassium and sodium currents and glutamate signal pathway.
abstract: In the present study, we established an in vitro model of hypoxic-ischemia via exposing primary neurons of newborn rats to oxygen-glucose deprivation (OGD) and observing the effects of genistein, a soybean isoflavone, on hypoxic-ischemic neuron viability, apoptosis, voltage-activated potassium (Kv) and sodium (Nav) currents, and glutamate receptor subunits. The results indicated that OGD exposure reduced the viability and increased the apoptosis of brain neurons. Meanwhile, OGD exposure caused changes in the current-voltage curves and current amplitude values of voltage-activated potassium and sodium currents; OGD exposure also decreased GluR2 expression and increased NR2 expression. However, genistein at least partially reversed the effects caused by OGD. The results suggest that hypoxic-ischemia-caused neuronal apoptosis/death is related to an increase in K(+) efflux, a decrease in Na(+) influx, a down-regulation of GluR2, and an up-regulation of NR2. Genistein may exert some neuroprotective effects via the modulation of Kv and Nav currents and the glutamate signal pathway, mediated by GluR2 and NR2.
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Ma
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Cong-Cong
authors.initials: CC
authors.lastname: He
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Tian
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Di
authors.initials: D
authors.lastname: An
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Heng
authors.affiliation: College of Life Sciences, Nankai University, Tianjin 300071, 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*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013779:Tetrodotoxin / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D024642:Potassium Channels, Voltage-Gated; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D061566:Voltage-Gated Sodium Channels; D018698:Glutamic Acid; D013779:Tetrodotoxin; D019833:Genistein; C104722:glutamate receptor ionotropic, AMPA 2
keywords: Genistein; Hypoxic-ischemia; Neuronal death; Voltage-gated currents; glutamate signal pathway