Erythrocyte Cytoskeletal-plasma Membrane Protein Network in Rett Syndrome: Effects of ω-3 Polyunsaturated Fatty Acids

Title:Erythrocyte Cytoskeletal-plasma Membrane Protein Network in Rett Syndrome: Effects of ω-3 Polyunsaturated Fatty Acids

Volume: 12 Issue: 4

Author(s): Assunta Gagliardi, Joussef Hayek, Lucia Ciccoli, Marcello Rossi, Jean-Marie Galano, Thierry Durand, Luca Bini, Mariangela Gentile, Eugenio Paccagnini, Alessandro Armini, Alessio Cortelazzo, Alessandra Pecorelli, Gloria Zollo, Cinzia Signorini, Silvia Leoncini, Alessandro Barducci, Roberto Leoncini, Roberto Guerranti and Claudio De Felice

Affiliation:

Keywords: Cytoskeletal-plasma membrane protein network, oxidative post-translational modifications, protein expression, rett syndrome, ω-3 polyunsaturated fatty acids.

Abstract: Rett syndrome (RTT) is a rare and severe neurodevelopmental disorder, mainly caused (~90-95% of cases) by loss-of-function mutations in the X-linked methyl-CpG-binding protein 2 gene. Recent studies indicate an important role of oxidative stress in damaging the RTT erythrocytes. The present study aims at demonstrating that the abnormal erythrocyte morphology observed in RTT (i.e., leptocytosis) is related to protein expression changes and oxidative posttranslational modifications (PTMs). Furthermore, we evaluated whether protein changes could be rescued following ω-3 polyunsaturated fatty acids (ω-3 PUFAs) supplementation. Erythrocytes from RTT patients, either on or off ω-3 PUFAs, were examined for oxidative PTMs, protein expression, protein-protein interaction and biophysical parameters. Significant (P < 0.05) expression changes and oxidative PTMs for 12 proteins were evidenced in RTT, and related to increased susceptibility of erythrocytes to mechanical stress (i.e., spectrin alpha and beta chains, ankyrin, band 3, protein 4.1, adducin, protein 4.2, 55 kDa protein, beta-actin, tropomodulin, aldolase and glyceraldehyde-3-phosphate dehydrogenase). Half of these proteins were rescued after ω-3 PUFAs supplementation. Our findings indicate the occurrence of a significant disruption in the RTT erythrocyte cytoskeletal-membrane protein network as the result of redox imbalance and protein expression changes, which appear to be partially rescued by ω-3 PUFAs.

Cite this article as:

Gagliardi Assunta, Hayek Joussef, Ciccoli Lucia, Rossi Marcello, Galano Jean-Marie, Durand Thierry, Bini Luca, Gentile Mariangela, Paccagnini Eugenio, Armini Alessandro, Cortelazzo Alessio, Pecorelli Alessandra, Zollo Gloria, Signorini Cinzia, Leoncini Silvia, Barducci Alessandro, Leoncini Roberto, Guerranti Roberto and Felice De Claudio, Erythrocyte Cytoskeletal-plasma Membrane Protein Network in Rett Syndrome: Effects of ω-3 Polyunsaturated Fatty Acids, Current Proteomics 2015; 12 (4) . https://dx.doi.org/10.2174/157016461204160119153511