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. 2005 Dec;25(8):1245–1254. doi: 10.1007/s10571-005-8501-2

Oxidative DNA Damage and Activation of c-Jun N-Terminal Kinase Pathway in Fibroblasts from Patients with Hereditary Spastic Paraplegia

Andreina Milano 1, Nicola Montesano Gesualdi 2, Raffaele Teperino 1, Franca Esposito 2, Sergio Cocozza 1, Paola Ungaro 3,✉
PMCID: PMC11529223  PMID: 16388335

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.

Keywords: reactive oxygen species, DNA damage, Comet assay, JNK phosphorylation, Western blotting

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