title: Two free radical pathways mediate chemical hypoxia-induced glutamate release in synaptosomes from the prefrontal cortex.
abstract: It has been known that the inhibition of mitochondrial cytochrome c oxidase is one of the earliest events occurring under hypoxia and this inhibition can lead to neuronal damages. Thus, the cytochrome c oxidase inhibitor sodium cyanide (NaCN) is widely used to produce a model of chemical hypoxia by inhibiting this enzyme. However, the downstream signaling pathways of the inhibition of the cytochrome c oxidase remain to be studied. In the present paper, we used sodium cyanide to mimic the inhibition of the mitochondrial cytochrome c oxidase and studied its effect on glutamate release in synaptosomes from the prefrontal cortex using on-line fluorimetry. We also further investigated the mechanisms underlying the enhancing effect of sodium cyanide on glutamate release using pharmacological approaches combined with other techniques. The results showed that sodium cyanide significantly increased glutamate release from synaptosomes of prefrontal cortex; the broad-spectrum free radical scavenger MnTBAP and melatonin completely abolished the effect of sodium cyanide on glutamate release; the H2O2-NMDA receptor pathway mediated one part, whereas the lipid peroxyl radicals-ATP synthase pathway mediated another part of the sodium cyanide-induced glutamate release; scavenging H2O2 and enhancing ATP synthase activity could completely abolish the sodium cyanide-induced glutamate release.
authors: State Key Laboratory of Medical Neurobiology, Shanghai Medical College and Institute of Brain Science, Fudan University, Shanghai, China.
authors: Yi
authors: Y
authors: Dong
authors: Wen
authors: W
authors: Zhang
authors: Bin
authors: B
authors: Lai
authors: Wen-Jie
authors: WJ
authors: Luan
authors: Yan-Hua
authors: YH
authors: Zhu
authors: Bing-Qiao
authors: BQ
authors: Zhao
authors: Ping
authors: P
authors: Zheng
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism; D000860:Hypoxia / Q000139:chemically induced / Q000378:metabolism*; D015227:Lipid Peroxidation; D008297:Male; D025261:Mitochondrial Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000648:ultrastructure; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012966:Sodium Cyanide / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D005609:Free Radicals; D016877:Oxidants; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C056639:2-amino-5-phosphopentanoic acid; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D025261:Mitochondrial Proton-Translocating ATPases; D014633:Valine; D012966:Sodium Cyanide