Abstract
1. Hereditary spastic paraplegia (HSP) is a genetically heterogeneous group of neurodegenerative disorders affecting 1 in 10,000 individuals. The present study was aimed to elucidate the role played by reactive oxygen species (ROS) in the pathogenesis of this disease. 2. To address this question we used 7-11 passaged fibroblasts from HSP patients to measure the extent of DNA damage induced by H2O2 treatment and to evaluate the JNK phosphorylation level after hydrogen peroxide and serum stimuli. 3. The present study demonstrates that HSP cells compared to controls are more sensitive to DNA damages induced by H2O2 treatment, and that JNK phosphorylation levels are increased in HSP fibroblasts compared to controls after hydrogen peroxide and serum stimuli. These results suggest a ROS-mediated pathogenetic mechanism for this disease.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Blood Proteins / pharmacology
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Cells, Cultured
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Culture Media / pharmacology
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DNA Damage / drug effects
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DNA Damage / physiology*
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Enzyme Activation / drug effects
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Enzyme Activation / physiology
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Fibroblasts / drug effects
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Fibroblasts / enzymology*
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Humans
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Hydrogen Peroxide / pharmacology
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Male
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Oxidative Stress / drug effects
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Oxidative Stress / physiology*
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Phosphorylation / drug effects
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Reactive Oxygen Species / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Spastic Paraplegia, Hereditary / enzymology*
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Spastic Paraplegia, Hereditary / genetics
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Spastic Paraplegia, Hereditary / physiopathology
Substances
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Blood Proteins
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Culture Media
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Reactive Oxygen Species
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Hydrogen Peroxide
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JNK Mitogen-Activated Protein Kinases