Calcium vs. iron-mediated processes in hydrogen peroxide toxicity to L929 cells: effects of glucose.
H2O2 toxicity was studied in L929 cells in the presence and absence of glucose. The data obtained in the absence of glucose suggest a Ca2+-dependent mechanism of cell injury. No evidence was found for any involvement of iron in the process. In particular, cell injury was unaffected by the intracellular iron chelators 2,2'-dipyridyl and deferoxamine or by the hydroxyl radical scavengers DMSO and DMPO. On the other hand, the intracellular Ca2+ chelator BAPTA/AM provided significant protection. The cytosolic Ca2+ level rapidly and consistently increased after H2O2 addition, prior to visible bleb formation and loss of cell viability. Additionally, GSH not only prevented cell death but also significantly decreased cytosolic calcium accumulation. In the presence of glucose, however, Ca2+ does not seem to play any role in H2O2 toxicity. Cell death is now mainly mediated by iron: the iron chelators and hydroxyl radical scavengers prevented cell injury, the increase in cytosolic Ca2+ was significantly less pronounced, and BAPTA/AM did not exert any protection under these conditions. Hence, the metabolic state of the L929 cells, as given by the availability of glucose, decisively determines the biochemical mechanism of H2O2 cell injury.
Lomonosova
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Institut für Physiologische Chemie, Universitätsklinikum, Essen, Germany.
Kirsch
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M
de Groot
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H
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology*; D016923:Cell Death; D002460:Cell Line; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D005978:Glutathione / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity*; D007501:Iron / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice
D002614:Chelating Agents; D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D004533:Egtazic Acid; D006861:Hydrogen Peroxide; D007501:Iron; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D005947:Glucose; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium