title: Glutamate release by an Na+ load and oxidative stress in nerve terminals: relevance to ischemia/reperfusion.
abstract: Previously we have reported that oxidative stress induced by hydrogen peroxide exacerbates the effect of an Na+ load in isolated nerve terminals, with a consequence of an ATP depletion, [Ca2+]i and [Na+]i deregulation, and collapse of mitochondrial membrane potential. In the present study, the release of glutamate in response to a combined effect of an [Na+] load and oxidative stress was measured in isolated nerve terminals over an incubation for 15 min. Exposure to hydrogen peroxide (100 micro m) had no effect on the release of glutamate, but significantly enhanced the Ca2+-independent glutamate release induced by a small [Na+] load achieved with 10 micro m veratridine. The effect of a larger Na+ load induced by 40 micro m veratridine was not further increased by hydrogen peroxide; in contrast the external Ca2+-dependent glutamate release was completely eliminated by the oxidant under this condition. The effects of oxidative stress superimposed on a Na+ load are consistent with at least two factors: (i) a relatively modest Na+ load induced by veratridine is augmented by H2O2 giving rise to an increased Ca2+-independent release of glutamate (ii) oxidative stress in combination with a larger Na+ load causes severe ATP depletion limiting the Ca2+-dependent vesicular glutamate release. Given the concurrent presence of an Na+ load and oxidative stress in ischemia/reperfusion these results indicate that the extent of the Na+ load developing during the ischemic period could determine the release of glutamate induced by an oxidative stress during reperfusion.
authors.affiliation: Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Tretter
authors.forename: Vera
authors.initials: V
authors.lastname: Adam-Vizi
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism*; D006168:Guinea Pigs; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*; D017729:Presynaptic Terminals / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism*; D012964:Sodium / Q000737:chemistry / Q000378:metabolism*; D013574:Synaptosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D014701:Veratridine / Q000494:pharmacology
chemical_list: D016877:Oxidants; D018698:Glutamic Acid; D014701:Veratridine; D000255:Adenosine Triphosphate; D012964:Sodium; D006861:Hydrogen Peroxide