title: Oxidative DNA damage and activation of c-Jun N-terminal kinase pathway in fibroblasts from patients with hereditary spastic paraplegia.
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.
authors.affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università degli Studi di Napoli Federico II, Naples, Italy.
authors.forename: Andreina
authors.initials: A
authors.lastname: Milano
authors.forename: Nicola
authors.initials: N
authors.lastname: Montesano Gesualdi
authors.forename: Raffaele
authors.initials: R
authors.lastname: Teperino
authors.forename: Franca
authors.initials: F
authors.lastname: Esposito
authors.forename: Sergio
authors.initials: S
authors.lastname: Cocozza
authors.forename: Paola
authors.initials: P
authors.lastname: Ungaro
mesh_terms: D001798:Blood Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D003470:Culture Media / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015419:Spastic Paraplegia, Hereditary / Q000201:enzymology* / Q000235:genetics / Q000503:physiopathology
chemical_list: D001798:Blood Proteins; D003470:Culture Media; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases