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: Zhao Liu, Yue-yang Huang, Yu-xiang Wang, Hong-gang Wang, Fei Deng, Bin Heng, Lai-hua Xie, Yan-qiang Liu
• Journal: Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) (J Trace Elem Med Biol) Vol. 31 Pg. 45-52 ( 2015) ISSN: 1878-3252 [Electronic] Germany
• PMID: 26004891 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier GmbH. All rights reserved.

Chemical References

• Chelating Agents
• Ethylenediamines
• Potassium Channels, Voltage-Gated
• Receptors, AMPA
• Glutamic Acid
• Glucose
• Zinc
• glutamate receptor ionotropic, AMPA 2
• N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
• Oxygen

Topics

• Animals
• Apoptosis (drug effects)
• Cell Death (drug effects)
• Cell Hypoxia (drug effects)
• Chelating Agents (pharmacology)
• Ethylenediamines (pharmacology)
• Glucose (metabolism)
• Glutamic Acid (metabolism)
• Oxygen (metabolism)
• PC12 Cells (drug effects)
• Potassium Channels, Voltage-Gated (metabolism)
• Rats
• Receptors, AMPA (metabolism)
• Zinc (metabolism)