Expression of the Na(+)/Ca(2+) exchanger ameliorates ionomycin-induced cell death.
PC12 cells were stably transfected with cDNA encoding the Na(+)/Ca(2+) exchanger (NCX1.4). A robust Na(+)-dependent Ca(2+) uptake confirmed the functional expression of the protein. When NCX1. 4 expressing cells (NO) and vector transfected control cells (VC) were exposed to 0.5-20 microM ionomycin for 6 h, a dose-dependent increase in LDH release was observed. LDH release was significantly reduced in NO when compared with VC. When either VC and NO were treated with 3 microM ionomycin and 1.1 mM EGTA, the increase in LDH release was nearly abolished. However, when VC and NO were treated with ionomycin and then EGTA was added 2 min later, LDH release remained elevated. These data suggest ionomycin-induced cell death was Ca(2+) dependent and expressing NCX1.4 may have ameliorated cell death by reducing elevated [Ca(2+)](I).
Wang
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Department of Biological Sciences, Edison Technology Institute, Athens, Ohio 45701, USA.
Chen
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Colvin
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology*; D007476:Ionophores / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis / Q000235:genetics*
D007476:Ionophores; D019831:Sodium-Calcium Exchanger; D015759:Ionomycin; D002118:Calcium