Calcium Enhances In Vitro Free Radical‐Induced Damage to Brain Synaptosomes, Mitochondria, and Cultured Spinal Cord Neurons
抄録
<jats:p><jats:bold>Abstract: </jats:bold> Preincubation of rat brain synaptosomes with xanthine and xanthine oxidase (X/XO) in Ca<jats:sup>2+</jats:sup>‐free Krebs buffer resulted in a 27% inhibition of synaptosomal γ‐aminobutyric acid (GABA) uptake. Addition of 1.5 m<jats:italic>M</jats:italic> CaCl<jats:sub>2</jats:sub> increased the inhibition with X/XO to 46%, and inhibition was essentially complete when the calcium ionophore A23187 also was included. In other studies, preincubation of purified rat brain mitochondria with the combination of X/XO and 4 μ<jats:italic>M</jats:italic> CaCl<jats:sub>2</jats:sub> produced a significant (38%) decrease in state 3 respiration with glutamate/malate as substrate that was not seen with either X/XO or Ca<jats:sup>2+</jats:sup> alone. Similar results were obtained using cultured mouse spinal cord neurons in which incubation with X/XO/ADP/FeCl<jats:sub>2</jats:sub> and A23187 produced membrane damage as assessed by a 32% reduction of neuronal Na<jats:sup>+</jats:sup>, K<jats:sup>+</jats:sup>‐ATPase activity. Neither X/XO/ADP/FeCl<jats:sub>2</jats:sub> nor A23187 alone caused detectable inhibition. These results demonstrate the synergistic damaging effect of free radicals and Ca<jats:sup>2+</jats:sup> on membrane function. In addition, they suggest that free radical‐induced peroxidation of membrane lipid, occurring focally during complete or nearly complete ischemia in vivo, could result in intense cellular perturbation when coupled with increased intracellular Ca<jats:sup>2+</jats:sup>.</jats:p>
収録刊行物
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- Journal of Neurochemistry
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Journal of Neurochemistry 45 (4), 1288-1293, 1985-10
Wiley
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詳細情報 詳細情報について
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- CRID
- 1362825895294125184
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- NII論文ID
- 30014580849
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- ISSN
- 14714159
- 00223042
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