Role of lipid metabolism in cell killing by calcium plus ionophore A23187
作者:
W. Thomas Shier,
Daniel J. Dubourdieu,
Huei‐Hsiang L. Wang,
期刊:
Journal of Biochemical Toxicology
(WILEY Available online 1991)
卷期:
Volume 6,
issue 1
页码: 7-17
ISSN:0887-2082
年代: 1991
DOI:10.1002/jbt.2570060103
出版商: Wiley Subscription Services, Inc., A Wiley Company
关键词: Ionophore;A23187;Calcium Ion;Phospholipids;Membranes;Cultured Cells;Permeabilization;Arachidonic Acid;Phosphatidylinositol 4,5‐Bisphosphate;Diacylglycerol
数据来源: WILEY
摘要:
AbstractCultured fibroblasts treated with divalent cation ionophore A23187 in the presence of extracellular calcium provide a useful model system for studying mechanisms of cell death associated with elevated intracellular calcium concentrations. Cell death induced by A23187 plus calcium can be conveniently monitored as membrane permeabilization to Trypan blue dye. Because lipids are a major component of cell membranes and play an important role in determining membrane permeability, the present study was initiated to identify changes in cell lipid composition that occur during membrane permeabilization induced by calcium plus A23187. The percent label in each of the major structural lipids in biosynthetically labeled NIH3T3 fibroblasts changed<10% during the time course of membrane permeabilization. During the course of membrane permeabilization there was significantly increased label in lysophosphatidylinositol and lysophosphatidylcholine and reduced label in phosphatidylinositol 4,5‐bisphosphate. The time course of these changes corresponded to that of the arachidonic acid release response stimulated by calcium plus A23187, not to the time course of membrane permeabilization, which occurs later. These observations are consistent with lipid metabolism induced by A23187 plus calcium playing only a possible regulatory or intermediatory role in membrane permeabilization, rather than causing direct permeabilization of the lipid phase of the membran
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