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Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia
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| Zeitschriftentitel: | The Journal of Neuroscience |
|---|---|
| Personen und Körperschaften: | , , , , |
| In: | The Journal of Neuroscience, 25, 2005, 49, S. 11256-11268 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Society for Neuroscience
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| Schlagwörter: |
| author_facet |
Luo, Jing Chen, Hai Kintner, Douglas B. Shull, Gary E. Sun, Dandan Luo, Jing Chen, Hai Kintner, Douglas B. Shull, Gary E. Sun, Dandan |
|---|---|
| author |
Luo, Jing Chen, Hai Kintner, Douglas B. Shull, Gary E. Sun, Dandan |
| spellingShingle |
Luo, Jing Chen, Hai Kintner, Douglas B. Shull, Gary E. Sun, Dandan The Journal of Neuroscience Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia General Neuroscience |
| author_sort |
luo, jing |
| spelling |
Luo, Jing Chen, Hai Kintner, Douglas B. Shull, Gary E. Sun, Dandan 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.3271-05.2005 <jats:p>Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup>exchanger isoform 1 (NHE1) is a major acid extrusion mechanism after intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to the disruption of Na<jats:sup>+</jats:sup>homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Three hours of oxygen and glucose deprivation (OGD) followed by 21 h of reoxygenation (REOX) led to 68 ± 10% cell death. Inhibition of NHE1 with the potent inhibitor cariporide (HOE 642) or genetic ablation of NHE1 reduced OGD-induced cell death by ∼40–50% (<jats:italic>p</jats:italic>< 0.05). In NHE1<jats:sup>+/+</jats:sup>neurons, OGD caused a twofold increase in [Na<jats:sup>+</jats:sup>]<jats:sub>i</jats:sub>, and 60 min REOX triggered a sevenfold increase. Genetic ablation of NHE1 or HOE 642 treatment had no effects on the OGD-mediated initial Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise but reduced the second phase of Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise by ∼40–50%. In addition, 60 min REOX evoked a 1.5-fold increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>in NHE1<jats:sup>+/+</jats:sup>neurons, which was abolished by inhibition of either NHE1 or reverse-mode operation of Na<jats:sup>+</jats:sup>/Ca<jats:sup>2+</jats:sup>exchange. OGD/REOX-mediated mitochondrial Ca<jats:sup>2+</jats:sup>accumulation and cytochrome<jats:italic>c</jats:italic>release were attenuated by inhibition of NHE1 activity. In an<jats:italic>in vivo</jats:italic>focal ischemic model, 2 h of left middle cerebral artery occlusion followed by 24 h of reperfusion induced 84.8 ± 8.0 mm<jats:sup>3</jats:sup>infarction in NHE1<jats:sup>+/+</jats:sup>mice. NHE1<jats:sup>+/+</jats:sup>mice treated with HOE 642 or NHE1 heterozygous mice exhibited a ∼33% decrease in infarct size (<jats:italic>p</jats:italic>< 0.05). These results imply that NHE1 activity disrupts Na<jats:sup>+</jats:sup>and Ca<jats:sup>2+</jats:sup>homeostasis and contributes to ischemic neuronal damage.</jats:p> Decreased Neuronal Death in Na<sup>+</sup>/H<sup>+</sup>Exchanger Isoform 1-Null Mice after<i>In Vitro</i>and<i>In Vivo</i>Ischemia The Journal of Neuroscience |
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Society for Neuroscience, 2005 |
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Society for Neuroscience, 2005 |
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luo2005decreasedneuronaldeathinnahexchangerisoform1nullmiceafterinvitroandinvivoischemia |
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2005 |
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Society for Neuroscience |
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The Journal of Neuroscience |
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49 |
| title |
Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_unstemmed |
Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_full |
Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_fullStr |
Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_full_unstemmed |
Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_short |
Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_sort |
decreased neuronal death in na<sup>+</sup>/h<sup>+</sup>exchanger isoform 1-null mice after<i>in vitro</i>and<i>in vivo</i>ischemia |
| topic |
General Neuroscience |
| url |
http://dx.doi.org/10.1523/jneurosci.3271-05.2005 |
| publishDate |
2005 |
| physical |
11256-11268 |
| description |
<jats:p>Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup>exchanger isoform 1 (NHE1) is a major acid extrusion mechanism after intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to the disruption of Na<jats:sup>+</jats:sup>homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Three hours of oxygen and glucose deprivation (OGD) followed by 21 h of reoxygenation (REOX) led to 68 ± 10% cell death. Inhibition of NHE1 with the potent inhibitor cariporide (HOE 642) or genetic ablation of NHE1 reduced OGD-induced cell death by ∼40–50% (<jats:italic>p</jats:italic>< 0.05). In NHE1<jats:sup>+/+</jats:sup>neurons, OGD caused a twofold increase in [Na<jats:sup>+</jats:sup>]<jats:sub>i</jats:sub>, and 60 min REOX triggered a sevenfold increase. Genetic ablation of NHE1 or HOE 642 treatment had no effects on the OGD-mediated initial Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise but reduced the second phase of Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise by ∼40–50%. In addition, 60 min REOX evoked a 1.5-fold increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>in NHE1<jats:sup>+/+</jats:sup>neurons, which was abolished by inhibition of either NHE1 or reverse-mode operation of Na<jats:sup>+</jats:sup>/Ca<jats:sup>2+</jats:sup>exchange. OGD/REOX-mediated mitochondrial Ca<jats:sup>2+</jats:sup>accumulation and cytochrome<jats:italic>c</jats:italic>release were attenuated by inhibition of NHE1 activity. In an<jats:italic>in vivo</jats:italic>focal ischemic model, 2 h of left middle cerebral artery occlusion followed by 24 h of reperfusion induced 84.8 ± 8.0 mm<jats:sup>3</jats:sup>infarction in NHE1<jats:sup>+/+</jats:sup>mice. NHE1<jats:sup>+/+</jats:sup>mice treated with HOE 642 or NHE1 heterozygous mice exhibited a ∼33% decrease in infarct size (<jats:italic>p</jats:italic>< 0.05). These results imply that NHE1 activity disrupts Na<jats:sup>+</jats:sup>and Ca<jats:sup>2+</jats:sup>homeostasis and contributes to ischemic neuronal damage.</jats:p> |
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| description | <jats:p>Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup>exchanger isoform 1 (NHE1) is a major acid extrusion mechanism after intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to the disruption of Na<jats:sup>+</jats:sup>homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Three hours of oxygen and glucose deprivation (OGD) followed by 21 h of reoxygenation (REOX) led to 68 ± 10% cell death. Inhibition of NHE1 with the potent inhibitor cariporide (HOE 642) or genetic ablation of NHE1 reduced OGD-induced cell death by ∼40–50% (<jats:italic>p</jats:italic>< 0.05). In NHE1<jats:sup>+/+</jats:sup>neurons, OGD caused a twofold increase in [Na<jats:sup>+</jats:sup>]<jats:sub>i</jats:sub>, and 60 min REOX triggered a sevenfold increase. Genetic ablation of NHE1 or HOE 642 treatment had no effects on the OGD-mediated initial Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise but reduced the second phase of Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise by ∼40–50%. In addition, 60 min REOX evoked a 1.5-fold increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>in NHE1<jats:sup>+/+</jats:sup>neurons, which was abolished by inhibition of either NHE1 or reverse-mode operation of Na<jats:sup>+</jats:sup>/Ca<jats:sup>2+</jats:sup>exchange. OGD/REOX-mediated mitochondrial Ca<jats:sup>2+</jats:sup>accumulation and cytochrome<jats:italic>c</jats:italic>release were attenuated by inhibition of NHE1 activity. In an<jats:italic>in vivo</jats:italic>focal ischemic model, 2 h of left middle cerebral artery occlusion followed by 24 h of reperfusion induced 84.8 ± 8.0 mm<jats:sup>3</jats:sup>infarction in NHE1<jats:sup>+/+</jats:sup>mice. NHE1<jats:sup>+/+</jats:sup>mice treated with HOE 642 or NHE1 heterozygous mice exhibited a ∼33% decrease in infarct size (<jats:italic>p</jats:italic>< 0.05). These results imply that NHE1 activity disrupts Na<jats:sup>+</jats:sup>and Ca<jats:sup>2+</jats:sup>homeostasis and contributes to ischemic neuronal damage.</jats:p> |
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| spelling | Luo, Jing Chen, Hai Kintner, Douglas B. Shull, Gary E. Sun, Dandan 0270-6474 1529-2401 Society for Neuroscience General Neuroscience http://dx.doi.org/10.1523/jneurosci.3271-05.2005 <jats:p>Na<jats:sup>+</jats:sup>/H<jats:sup>+</jats:sup>exchanger isoform 1 (NHE1) is a major acid extrusion mechanism after intracellular acidosis. We hypothesized that stimulation of NHE1 after cerebral ischemia contributes to the disruption of Na<jats:sup>+</jats:sup>homeostasis and neuronal death. In the present study, expression of NHE1 was detected in cultured mouse cortical neurons. Three hours of oxygen and glucose deprivation (OGD) followed by 21 h of reoxygenation (REOX) led to 68 ± 10% cell death. Inhibition of NHE1 with the potent inhibitor cariporide (HOE 642) or genetic ablation of NHE1 reduced OGD-induced cell death by ∼40–50% (<jats:italic>p</jats:italic>< 0.05). In NHE1<jats:sup>+/+</jats:sup>neurons, OGD caused a twofold increase in [Na<jats:sup>+</jats:sup>]<jats:sub>i</jats:sub>, and 60 min REOX triggered a sevenfold increase. Genetic ablation of NHE1 or HOE 642 treatment had no effects on the OGD-mediated initial Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise but reduced the second phase of Na<jats:sup>+</jats:sup><jats:sub>i</jats:sub>rise by ∼40–50%. In addition, 60 min REOX evoked a 1.5-fold increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>in NHE1<jats:sup>+/+</jats:sup>neurons, which was abolished by inhibition of either NHE1 or reverse-mode operation of Na<jats:sup>+</jats:sup>/Ca<jats:sup>2+</jats:sup>exchange. OGD/REOX-mediated mitochondrial Ca<jats:sup>2+</jats:sup>accumulation and cytochrome<jats:italic>c</jats:italic>release were attenuated by inhibition of NHE1 activity. In an<jats:italic>in vivo</jats:italic>focal ischemic model, 2 h of left middle cerebral artery occlusion followed by 24 h of reperfusion induced 84.8 ± 8.0 mm<jats:sup>3</jats:sup>infarction in NHE1<jats:sup>+/+</jats:sup>mice. NHE1<jats:sup>+/+</jats:sup>mice treated with HOE 642 or NHE1 heterozygous mice exhibited a ∼33% decrease in infarct size (<jats:italic>p</jats:italic>< 0.05). These results imply that NHE1 activity disrupts Na<jats:sup>+</jats:sup>and Ca<jats:sup>2+</jats:sup>homeostasis and contributes to ischemic neuronal damage.</jats:p> Decreased Neuronal Death in Na<sup>+</sup>/H<sup>+</sup>Exchanger Isoform 1-Null Mice after<i>In Vitro</i>and<i>In Vivo</i>Ischemia The Journal of Neuroscience |
| spellingShingle | Luo, Jing, Chen, Hai, Kintner, Douglas B., Shull, Gary E., Sun, Dandan, The Journal of Neuroscience, Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia, General Neuroscience |
| title | Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_full | Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_fullStr | Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_full_unstemmed | Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_short | Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| title_sort | decreased neuronal death in na<sup>+</sup>/h<sup>+</sup>exchanger isoform 1-null mice after<i>in vitro</i>and<i>in vivo</i>ischemia |
| title_unstemmed | Decreased Neuronal Death in Na+/H+Exchanger Isoform 1-Null Mice afterIn VitroandIn VivoIschemia |
| topic | General Neuroscience |
| url | http://dx.doi.org/10.1523/jneurosci.3271-05.2005 |