Involvement of Na<sup>+</sup>–Ca<sup>2+</sup> Exchanger in Reperfusion‐induced Delayed Cell Death of Cultured Rat Astrocytes
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<jats:title>Abstract</jats:title><jats:p>In some cells, Ca<jats:sup>2+</jats:sup> depletion induces an increase in intracellular Ca<jats:sup>2+</jats:sup> ([Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub>) after reperfusion with Ca<jats:sup>2+</jats:sup>‐containing solution, but the mechanism for the reperfusion injury is not fully elucidated. Using an antisense strategy we studied the role of the Na<jats:sup>+</jats:sup>‐Ca<jats:sup>2+</jats:sup> exchanger in reperfusion injury in cultured rat astrocytes. When astrocytes were perfused in Ca<jats:sup>2+</jats:sup>‐free medium for 15–60 min, a persistent increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> was observed immediately after reperfusion with Ca<jats:sup>2+</jats:sup>‐containing medium, and the number of surviving cells decreased 3–5 days latter. The increase in [Ca<jats:sup>2+</jats:sup>]<jats:sub>i</jats:sub> was enhanced by low extracellular Na<jats:sup>+</jats:sup> ([Na<jats:sup>+</jats:sup>]<jats:sub>o</jats:sub>) during reperfusion and blocked by the inhibitors of the Na<jats:sup>+</jats:sup>‐Ca<jats:sup>2+</jats:sup> exchanger amiloride and 3,4‐dichlorobenzamil, but not by the Ca<jats:sup>2+</jats:sup> channel antagonists nifedipine, Cd<jats:sup>2+</jats:sup> and Ni<jats:sup>2+</jats:sup>. Treatment of astrocytes with antisense, but not sense, oligodeoxynucleotide to the Na<jats:sup>+</jats:sup>‐Ca<jats:sup>2+</jats:sup> exchanger decreased Na<jats:sup>+</jats:sup>–Ca<jats:sup>2+</jats:sup> exchanger protein level and exchange activity. The antisense oligomer attenuated reperfusion‐induced increase in [Ca<jats:sup>2+</jats:sup>]<jats:sup>i</jats:sup> and cell toxicity. The Na<jats:sup>+</jats:sup>‐Ca<jats:sup>2+</jats:sup> exchange inhibitors 3,4‐dichlorobenzamil and ascorbic acid protected astrocytes from reperfusion injury partially, while the stimulators sodium nitroprusside and 8‐bromo‐cyclic GMP and low [Na<jats:sup>+</jats:sup>]<jats:sub>o</jats:sub> exacerbated the injury. Pretreatment of astrocytes with ouabain and monensin caused similar delayed glial cell death. These findings suggest that Ca<jats:sup>2+</jats:sup> entry via the Na<jats:sup>+</jats:sup>–Ca<jats:sup>2+</jats:sup> exchanger plays an important role in reperfusion‐induced delayed glial cell death.</jats:p>
収録刊行物
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- European Journal of Neuroscience
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European Journal of Neuroscience 8 (5), 951-958, 1996-05
Wiley
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詳細情報
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- CRID
- 1361981470962508160
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- NII論文ID
- 30014386107
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- ISSN
- 14609568
- 0953816X
- http://id.crossref.org/issn/0953816X
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