Redox Imbalance and Morphological Changes in Skin Fibroblasts in Typical Rett Syndrome

• Main Authors: Cinzia Signorini, Silvia Leoncini, Claudio De Felice, Alessandra Pecorelli, Ilaria Meloni, Francesca Ariani, Francesca Mari, Sonia Amabile, Eugenio Paccagnini, Mariangela Gentile, Giuseppe Belmonte, Gloria Zollo, Giuseppe Valacchi, Thierry Durand, Jean-Marie Galano, Lucia Ciccoli, Alessandra Renieri, Joussef Hayek
• Format: Article
• Language: English
• Published: Hindawi Limited 2014-01-01
• Series: Oxidative Medicine and Cellular Longevity
• Online Access: http://dx.doi.org/10.1155/2014/195935
• ISSN: 1942-0900; 1942-0994

Evidence of oxidative stress has been reported in the blood of patients with Rett syndrome (RTT), a neurodevelopmental disorder mainly caused by mutations in the gene encoding the Methyl-CpG-binding protein 2. Little is known regarding the redox status in RTT cellular systems and its relationship with the morphological phenotype. In RTT patients (n = 16) we investigated four different oxidative stress markers, F2-Isoprostanes (F2-IsoPs), F4-Neuroprostanes (F4-NeuroPs), nonprotein bound iron (NPBI), and (4-HNE PAs), and glutathione in one of the most accessible cells, that is, skin fibroblasts, and searched for possible changes in cellular/intracellular structure and qualitative modifications of synthesized collagen. Significantly increased F4-NeuroPs (12-folds), F2-IsoPs (7.5-folds) NPBI (2.3-folds), 4-HNE PAs (1.48-folds), and GSSG (1.44-folds) were detected, with significantly decreased GSH (−43.6%) and GSH/GSSG ratio (−3.05 folds). A marked dilation of the rough endoplasmic reticulum cisternae, associated with several cytoplasmic multilamellar bodies, was detectable in RTT fibroblasts. Colocalization of collagen I and collagen III, as well as the percentage of type I collagen as derived by semiquantitative immunofluorescence staining analyses, appears to be significantly reduced in RTT cells. Our findings indicate the presence of a redox imbalance and previously unrecognized morphological skin fibroblast abnormalities in RTT patients.