Title:Erythrocyte Cytoskeletal-plasma Membrane Protein Network in Rett Syndrome: Effects of ω-3 Polyunsaturated Fatty Acids
VOLUME: 12 ISSUE: 4
Author(s):Alessio Cortelazzo, Claudio De Felice, Roberto Guerranti, Roberto Leoncini, Alessandro Barducci, Silvia Leoncini, Cinzia Signorini, Gloria Zollo, Alessandra Pecorelli, Assunta Gagliardi, Alessandro Armini, Eugenio Paccagnini, Mariangela Gentile, Luca Bini, Thierry Durand, Jean-Marie Galano, Marcello Rossi, Lucia Ciccoli and Joussef Hayek
Affiliation:Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Viale Bracci 16, 53100 Siena, Italy.
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.
