Display options
Cite
Cervellati C, Sticozzi C, Romani A, et al. Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage. Biochim Biophys Acta. 2015;1852(10):2066-74doi: 10.1016/j.bbadis.2015.07.014.
Cervellati, C., Sticozzi, C., Romani, A., Belmonte, G., De Rasmo, D., Signorile, A., Cervellati, F., Milanese, C., Mastroberardino, P. G., Pecorelli, A., Savelli, V., Forman, H. J., Hayek, J., & Valacchi, G. (2015). Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage. Biochimica et biophysica acta, 1852(10), 2066-74. https://doi.org/10.1016/j.bbadis.2015.07.014
Cervellati, Carlo, et al. "Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage." Biochimica et biophysica acta vol. 1852,10 (2015): 2066-74. doi: https://doi.org/10.1016/j.bbadis.2015.07.014
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. Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage. Biochim Biophys Acta. 2015 Oct;1852(10):2066-74. doi: 10.1016/j.bbadis.2015.07.014. Epub 2015 Jul 17. PMID: 26189585.
Copy Download .nbib Format: NLM
Share it on

Biochim Biophys Acta. 2015 Oct;1852(10):2066-74. doi: 10.1016/j.bbadis.2015.07.014. Epub 2015 Jul 17.

Impaired enzymatic defensive activity, mitochondrial dysfunction and proteasome activation are involved in RTT cell oxidative damage.

Biochimica et biophysica acta

Carlo Cervellati, Claudia Sticozzi, Arianna Romani, Giuseppe Belmonte, Domenico De Rasmo, Anna Signorile, Franco Cervellati, Chiara Milanese, Pier Giorgio Mastroberardino, Alessandra Pecorelli, Vinno Savelli, Henry J Forman, Joussef Hayek, Giuseppe Valacchi

Affiliations

  1. Department of Biomedical and Specialist Surgical Sciences, Section of Medical Biochemistry, Molecular Biology and Genetics, University of Ferrara, Ferrara, Italy.
  2. Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy.
  3. Institute of Biomembrane and Bioenergetics, CNR, Bari 70124, Italy.
  4. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", Bari 70124, Italy.
  5. Department of Genetics, Erasmus University Medical Center Rotterdam, the Netherlands.
  6. Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.
  7. Dipartimento di Scienze Mediche, Chirurgiche e Neuroscienze, Universita' di Siena, 53100 Siena, Italy.
  8. Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA; Life and Environmental Sciences Unit, University of California at Merced, Merced, CA 95344, USA.
  9. Department of Life Sciences and Biotechnology, University of Ferrara, 44121 Ferrara, Italy; Department of Food and Nutrition, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: [email protected].

PMID: 26189585 DOI: 10.1016/j.bbadis.2015.07.014

Abstract

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.

Copyright © 2015 Elsevier B.V. All rights reserved.

Keywords: 4HNE; Glutathione peroxidase; NADPH oxidase; Oxidative stress; Superoxide dismutase thioredoxin-reductases

Publication Types