Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage
| العنوان: | Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage |
|---|---|
| المؤلفون: | Domenico De Rasmo, Henry Jay Forman, Claudia Sticozzi, Pier G. Mastroberardino, Vinno Savelli, Alessandra Pecorelli, Franco Cervellati, Arianna Romani, Giuseppe Valacchi, Giuseppe Belmonte, Chiara Milanese, Anna Signorile, Carlo Cervellati, Joussef Hayek |
| المساهمون: | Molecular Genetics |
| المصدر: | Biochimica et biophysica acta, vol 1852, iss 10 Pt A Biochimica et Biophysica Acta-Molecular Basis of Disease, 1852(10), 2066-2074. Elsevier Biochimica et biophysica acta. Molecular basis of disease (2015). info:cnr-pdr/source/autori:Cervellati C, Sticozzi C, Romani A, Belmonte G, De Rasmo D, Signorile A, Cervellati F, Milanese C, Mastroberardino PG, Pecorelli A, Savelli V, Forman HJ, Hayek J, Valacchi G./titolo:Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage/doi:/rivista:Biochimica et biophysica acta. Molecular basis of disease/anno:2015/pagina_da:/pagina_a:/intervallo_pagine:/volume Europe PubMed Central |
| بيانات النشر: | eScholarship, University of California, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | congenital, hereditary, and neonatal diseases and abnormalities, Rett syndrome, oxidative stress, mitochondria, NADPH oxidase, glutathione peroxidase, superoxide dismutase thioredoxin-reductases, 4HNE, Neurodegenerative, medicine.disease_cause, NO, Superoxide dismutase, Rare Diseases, Clinical Research, medicine, 2.1 Biological and endogenous factors, Aetiology, Molecular Biology, chemistry.chemical_classification, biology, Glutathione peroxidase, Biological Sciences, medicine.disease, Oxidative stress, Superoxide dismutase thioredoxin-reductases, Cell biology, Proteasome, Mitochondrial biogenesis, chemistry, Physical Sciences, biology.protein, Molecular Medicine, Thioredoxin |
| الوصف: | A strong correlation between oxidative stress (OS) and Rett syndrome (RTT), a rare neurodevelopmental disorder affecting females in the 95% of the cases, has been well documented although the source of OS and the effect of a redox imbalance in this pathology has not been yet investigated. Using freshly isolated skin fibroblasts from RTT patients and healthy subjects, we have demonstrated in RTT cells high levels of H2O2 and HNE protein adducts. These findings correlated with the constitutive activation of NADPH-oxidase (NOX) and that was prevented by a NOX inhibitor and iron chelator pre-treatment, showing its direct involvement. In parallel, we demonstrated an increase in mitochondrial oxidant production, altered mitochondrial biogenesis and impaired proteasome activity in RTT samples. Further, we found that the key cellular defensive enzymes: glutathione peroxidase, superoxide dismutase and thioredoxin reductases activities were also significantly lower in RTT. Taken all together, our findings suggest that the systemic OS levels in RTT can be a consequence of both: increased endogenous oxidants as well as altered mitochondrial biogenesis with a decreased activity of defensive enzymes that leads to posttranslational oxidant protein modification and a proteasome activity impairment. (C) 2015 Elsevier B.V. All rights reserved. |
| تدمد: | 0925-4439 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cd82b80c3eca9cd97eedc58a297cc72b https://escholarship.org/uc/item/68r8f5jb |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....cd82b80c3eca9cd97eedc58a297cc72b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09254439 |
|---|