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

Cinzia Signorini (1) , Silvia Leoncini (1, 2) , Claudio de Felice (3) , Alessandra Pecorelli (1, 2) , Ilaria Meloni (4) , Francesca Ariani (4) , Francesca Mari (4) , Sonia Amabile (4) , Eugenio Paccagnini (5) , Mariangela Gentile (5) , Guiseppe Belmonte (6) , Gloria Zollo (1, 2) , Giuseppe Valacchi (7) , Thierry Durand (8) , Jean-Marie Galano (8) , Lucia Ciccoli (1) , Alessandra Renieri (4, 9) , Joussef Hayek (2)

1 Department of Molecular and Developmental Medicine
2 Child Neuropsychiatry Unit
3 Neonatal Intensive Care Unit
4 Medical Genetics
5 Department of Life Sciences
6 Department of Medicine Surgery and Neuroscience
7 Department of Life Sciences and Biotechnologies
8 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
9 Genetica Medica

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.

Mots clés: Rett syndrome; RTT; neurodevelopmental; mutations; gene; F2-Isoprostanes; F2-IsoPs; F4-Neuroprostanes; F4-NeuroPs; NPBI; GSH; GSSG

Domaines: Chimie organique

Cinzia Signorini, Silvia Leoncini, Claudio de Felice, Alessandra Pecorelli, Ilaria Meloni, et al.. Redox Imbalance and Morphological Changes in Skin Fibroblasts in Typical Rett Syndrome.. Oxidative Medicine and Cellular Longevity, 2014, 2014, pp.ID 195935. ⟨10.1155/2014/195935⟩. ⟨hal-01058127⟩