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+-d ependent mechanism of cell injury. No evidence was found for any invol vement of iron in the process. In particular, cell injury was unaffect ed by the intracellular iron chelators 2,2'-dipyridyl and deferoxamine or by the hydroxyl radical scavengers DMSO and DMPO. On the other han d, the intracellular Ca2+ chelator BAPTA/AM provided significant prote ction. The cytosolic Ca2+ level rapidly and consistently increased aft er H2O2 addition, prior to visible bleb formation and loss of cell via bility. Additionally, GSH not only prevented cell death but also signi ficantly 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 hy droxyl radical scavengers prevented cell injury, the increase in cytos olic Ca2+ was significantly less pronounced, and BAPTA/AM did not exer t any protection under these conditions. Hence, the metabolic state of the L929 cells, as given by the availability of glucose, decisively d etermines the biochemical mechanism of H2O2 cell injury.