title: Involvement of Na+-Ca2+ exchanger in reperfusion-induced delayed cell death of cultured rat astrocytes.
abstract: In some cells, Ca2+ depletion induces an increase in intracellular Ca2+ ([Ca2+]i) after reperfusion with Ca2+-containing solution, but the mechanism for the reperfusion injury is not fully elucidated. Using an antisense strategy we studied the role of the Na+-Ca2+ exchanger in reperfusion injury in cultured rat astrocytes. When astrocytes were perfused in Ca2+-free medium for 15-60 min, a persistent increase in [Ca2+]i was observed immediately after reperfusion with Ca2+-containing medium, and the number of surviving cells decreased 3-5 days later. The increase in [Ca2+]i was enhanced by low extracellular Na+ ([Na+]0) during reperfusion and blocked by the inhibitors of the Na+-Ca2+ exchanger amiloride and 3, 4-dichlorobenzamil, but not by the Ca2+ channel antagonists nifedipine, Ca2+ and Ni2+. Treatment of astrocytes with antisense, but not sense, oligodeoxynucleotide to the Na+-Ca2+ exchanger decreased Na+-Ca2+ exchanger protein level and exchange activity. The antisense oligomer attenuated reperfusion-induced increase in [Ca2+]i and cell toxicity. The Na+-Ca2+ 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+]0 exacerbated the injury. Pretreatment of astrocytes with ouabain and monensin caused similar delayed glial cell death. These findings suggest that Ca2+ entry via the Na+-Ca2+ exchanger plays an important role in reperfusion-induced delayed glial cell death.
authors: Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565, Japan.
authors: T
authors: T
authors: Matsuda
authors: K
authors: K
authors: Takuma
authors: E
authors: E
authors: Nishiguchi
authors: H
authors: H
authors: Hashimoto
authors: J
authors: J
authors: Azuma
authors: A
authors: A
authors: Baba
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D012964:Sodium; D019831:Sodium-Calcium Exchanger; D013997:Time Factors
chemical_list: D002121:Calcium Channel Blockers; D002352:Carrier Proteins; D018696:Neuroprotective Agents; D019831:Sodium-Calcium Exchanger; C041470:3',4'-dichlorobenzamil; D000584:Amiloride; D012964:Sodium; D009543:Nifedipine; D002118:Calcium