Abstract
Reactive oxygen species (ROS) mediate apoptosis in a number of cell types. We studied the role that ROS play in activated T cell apoptosis by activating T cells in vivo and then culturing them for a short time. Activated T cells died independently of Fas and TNF alpha. Their death was characterized by rapid loss of mitochondrial transmembrane potential (delta psi(m)), caspase-dependent DNA fragmentation, and superoxide generation. A superoxide dismutase mimetic, Mn (III) tetrakis (5, 10, 15, 20-benzoic acid) porphyrin (MnTBAP), protected T cells from superoxide generation, caspase-dependent DNA loss, loss of delta psi(m), and cell death. These results indicate that ROS can regulate signals involved in caspase activation and apoptosis and may contribute to peripheral T cell deletion.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Apoptosis / immunology*
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Caspases / metabolism
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Caspases / physiology
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Enzyme Activation / drug effects
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Enzyme Activation / immunology
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Female
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Free Radical Scavengers / pharmacology
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Leukemia L1210
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Lymphocyte Activation* / drug effects
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Manganese / pharmacology
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Membrane Potentials / drug effects
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Membrane Potentials / immunology
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Metalloporphyrins / pharmacology
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Mice
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Mice, Inbred C57BL
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Mitochondria / drug effects
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Mitochondria / physiology
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Reactive Oxygen Species / physiology*
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Superantigens / pharmacology
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T-Lymphocytes / physiology*
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Tumor Necrosis Factor-alpha / pharmacology
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fas Receptor / pharmacology
Substances
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Free Radical Scavengers
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Metalloporphyrins
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Reactive Oxygen Species
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Superantigens
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Tumor Necrosis Factor-alpha
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fas Receptor
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manganese(III)-tetrakis(4-benzoic acid)porphyrin
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Manganese
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Caspases