Cellular and Molecular Neurobiology

, Volume 37, Issue 2, pp 235–250 | Cite as

TPEN, a Specific Zn2+ Chelator, Inhibits Sodium Dithionite and Glucose Deprivation (SDGD)-Induced Neuronal Death by Modulating Apoptosis, Glutamate Signaling, and Voltage-Gated K+ and Na+ Channels

  • Feng Zhang
  • Xue-ling Ma
  • Yu-xiang Wang
  • Cong-cong He
  • Kun Tian
  • Hong-gang Wang
  • Di An
  • Bin Heng
  • Lai-hua Xie
  • Yan-qiang Liu
Original Research


Hypoxia–ischemia-induced neuronal death is an important pathophysiological process that accompanies ischemic stroke and represents a major challenge in preventing ischemic stroke. To elucidate factors related to and a potential preventative mechanism of hypoxia–ischemia-induced neuronal death, primary neurons were exposed to sodium dithionite and glucose deprivation (SDGD) to mimic hypoxic–ischemic conditions. The effects of N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN), a specific Zn2+-chelating agent, on SDGD-induced neuronal death, glutamate signaling (including the free glutamate concentration and expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor (GluR2) and N-methyl-d-aspartate (NMDA) receptor subunits (NR2B), and voltage-dependent K+ and Na+ channel currents were also investigated. Our results demonstrated that TPEN significantly suppressed increases in cell death, apoptosis, neuronal glutamate release into the culture medium, NR2B protein expression, and I K as well as decreased GluR2 protein expression and Na+ channel activity in primary cultured neurons exposed to SDGD. These results suggest that TPEN could inhibit SDGD-induced neuronal death by modulating apoptosis, glutamate signaling (via ligand-gated channels such as AMPA and NMDA receptors), and voltage-gated K+ and Na+ channels in neurons. Hence, Zn2+ chelation might be a promising approach for counteracting the neuronal loss caused by transient global ischemia. Moreover, TPEN could represent a potential cell-targeted therapy.


Sodium dithionite Glucose deprivation TPEN Neuronal death Glutamate signal path Voltage-gated channel 



This work was supported by the National Natural Science Foundation of China (No. 31272317), the Natural Science Foundation of Tianjin City (15JCYBJC24500), and the 111 Project (B08011).

Compliance with Ethical Standards

Conflicts of interest

There are no conflicts of interest to declare.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Feng Zhang
    • 1
  • Xue-ling Ma
    • 1
  • Yu-xiang Wang
    • 1
  • Cong-cong He
    • 1
  • Kun Tian
    • 1
  • Hong-gang Wang
    • 1
  • Di An
    • 1
  • Bin Heng
    • 1
  • Lai-hua Xie
    • 2
  • Yan-qiang Liu
    • 1
  1. 1.College of Life SciencesNankai UniversityTianjinPeople’s Republic of China
  2. 2.Department of Cell Biology and Molecular Medicine, New Jersey Medical SchoolRutgers, The State University of New JerseyNew BrunswickUSA

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