Glutamine-mediated protection from neuronal cell death depends on mitochondrial activity

Neuroscience Letters
Elena V StelmashookN K Isaev

Abstract

The specific aim of this study was to elucidate the role of mitochondria in a neuronal death caused by different metabolic effectors and possible role of intracellular calcium ions ([Ca(2+)](i)) and glutamine in mitochondria- and non-mitochondria-mediated cell death. Inhibition of mitochondrial complex I by rotenone was found to cause intensive death of cultured cerebellar granule neurons (CGNs) that was preceded by an increase in intracellular calcium concentration ([Ca(2+)](i)). The neuronal death induced by rotenone was significantly potentiated by glutamine. In addition, inhibition of Na/K-ATPase by ouabain also caused [Ca(2+)](i) increase, but it induced neuronal cell death only in the absence of glucose. Treatment with glutamine prevented the toxic effect of ouabain and decreased [Ca(2+)](i). Blockade of ionotropic glutamate receptors prevented neuronal death and significantly decreased [Ca(2+)](i), demonstrating that toxicity of rotenone and ouabain was at least partially mediated by activation of these receptors. Activation of glutamate receptors by NMDA increased [Ca(2+)](i) and decreased mitochondrial membrane potential leading to markedly decreased neuronal survival under glucose deprivation. Glutamine treatment unde...Continue Reading

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Citations

May 18, 2011·The International Journal of Neuroscience·E V StelmashookL G Khaspekov
Nov 15, 2011·Brain Research Bulletin·Nickolay K IsaevElena V Stelmashook
May 23, 2015·Frontiers in Neuroscience·Danielle M OsborneEwan C McNay
May 24, 2017·Toxicology Mechanisms and Methods·Xiao-Wen JiangWen-Hui Yu
Jul 6, 2014·Physiological Reviews·Dmitry B ZorovSteven J Sollott
Sep 30, 2016·Biochemistry. Biokhimii︠a︡·E V StelmashookN K Isaev
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Mingyong ZhangYifeng Chai

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