Abstract
Effects of methotrexate (MTX) on mitochondrial oxidative metabolism and ion transport were studied. MTX decreases the membrane potential (delta psi) upon energization of the mitochondrial membrane by NAD+-linked substrates and decreases the amplitude and velocity of swelling induced by glutamate and alpha-ketoglutarate. MTX also has an inhibitory effect on the activities of the oxidation enzymes of NAD+-linked substrates without interfering with the oxidation systems of FAD-linked substrates. The effects of MTX could be interpreted as a consequence of a decrease in the ionic conductivity of the mitochondrial inner membrane.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Glutamate Dehydrogenase / metabolism
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Glycerolphosphate Dehydrogenase / metabolism
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In Vitro Techniques
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Ions / metabolism
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Isocitrate Dehydrogenase / metabolism
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Ketoglutarate Dehydrogenase Complex / metabolism
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Malate Dehydrogenase / metabolism
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Male
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Membrane Potentials / drug effects
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Methotrexate / pharmacology*
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Mitochondria, Liver / drug effects
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Mitochondria, Liver / enzymology
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Mitochondria, Liver / metabolism*
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Mitochondrial Swelling / drug effects
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NAD / metabolism
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Oxidation-Reduction
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Rats
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Succinate Dehydrogenase / metabolism
Substances
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Ions
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NAD
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Glycerolphosphate Dehydrogenase
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Malate Dehydrogenase
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Isocitrate Dehydrogenase
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Ketoglutarate Dehydrogenase Complex
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Succinate Dehydrogenase
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Glutamate Dehydrogenase
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Methotrexate