Peroxynitrite promotes mitochondrial permeability transition-dependent rapid U937 cell necrosis: survivors proliferate with kinetics superimposable on those of untreated cells.
A short term exposure to peroxynitrite promotes a time- and concentration-dependent lethal response in U937 cells. The mode of cell death was necrosis and rapid (within minutes) cell lysis was found to occur via a mechanism involving mitochondrial permeability transition. Apoptosis was not detected in cells exposed to low levels of peroxynitrite, or in cells which survived a treatment with toxic amounts of peroxynitrite, neither after the 60 min exposure nor following increasing time intervals of growth in fresh culture medium. Rather, cells treated with peroxynitrite concentrations which were not immediately lethal, as well as the survivors of treatments with toxic levels of peroxynitrite, proliferated with kinetics superimposable on those observed in untreated cells.
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Istituto di Farmacologia e Farmacognosia, Università di Urbino, Via S. Chiara, 27, 61029 - Urbino (PU), Italy.
Tommasini
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Cantoni
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D000975:Antioxidants / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D007700:Kinetics; D008715:Methionine / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009336:Necrosis; D009566:Nitrates / Q000494:pharmacology*; D010539:Permeability; D020298:U937 Cells
D000975:Antioxidants; D002839:Chromans; D009566:Nitrates; C039642:peroxynitric acid; D016572:Cyclosporine; D008715:Methionine; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid