Abstract
Recombinant human mitochondrial transcription factor A protein (rhTFAM) was evaluated for its acute effects on cultured cells and chronic effects in mice. Fibroblasts incubated with rhTFAM acutely increased respiration in a chloramphenicol-sensitive manner. SH-SY5Y cells showed rhTFAM concentration-dependent reduction of methylpyridinium (MPP(+))-induced oxidative stress and increases in lowered ATP levels and viability. Mice treated with weekly i.v. rhTFAM showed increased mitochondrial gene copy number, complex I protein levels and ATP production rates; oxidative damage to proteins was decreased ~50%. rhTFAM treatment improved motor recovery rate after treatment with MPTP and dose-dependently improved survival in the lipopolysaccharide model of endotoxin sepsis.
Copyright © 2010 Elsevier B.V. and Mitochondria Research Society. All rights reserved.
MeSH terms
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
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Adenosine Triphosphate / biosynthesis*
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Animals
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Cell Line, Tumor
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Cell Respiration / drug effects
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Cell Survival
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DNA, Mitochondrial / drug effects
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DNA, Mitochondrial / genetics
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DNA, Mitochondrial / metabolism
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DNA-Binding Proteins / administration & dosage
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / pharmacology*
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Endotoxemia / drug therapy
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Endotoxemia / mortality*
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Fibroblasts / physiology
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Humans
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Male
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Mice
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Mice, Inbred C57BL
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Mitochondria / drug effects
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Mitochondria / metabolism*
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Mitochondrial Proteins / administration & dosage
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Mitochondrial Proteins / pharmacology*
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Motor Activity / drug effects
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Motor Activity / physiology*
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Neurons / drug effects
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Neurons / metabolism
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Neurons / physiology
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Oxidative Stress / drug effects*
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Recombinant Proteins / pharmacology*
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Transcription Factors / administration & dosage
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / pharmacology*
Substances
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DNA, Mitochondrial
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DNA-Binding Proteins
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Mitochondrial Proteins
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Recombinant Proteins
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Transcription Factors
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mitochondrial transcription factor A
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Adenosine Triphosphate
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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine