title: Beta-actin deficiency with oxidative posttranslational modifications in Rett syndrome erythrocytes: insights into an altered cytoskeletal organization.
abstract: Beta-actin, a critical player in cellular functions ranging from cell motility and the maintenance of cell shape to transcription regulation, was evaluated in the erythrocyte membranes from patients with typical Rett syndrome (RTT) and methyl CpG binding protein 2 (MECP2) gene mutations. RTT, affecting almost exclusively females with an average frequency of 1∶10,000 female live births, is considered the second commonest cause of severe cognitive impairment in the female gender. Evaluation of beta-actin was carried out in a comparative cohort study on red blood cells (RBCs), drawn from healthy control subjects and RTT patients using mass spectrometry-based quantitative analysis. We observed a decreased expression of the beta-actin isoforms (relative fold changes for spots 1, 2 and 3: -1.82±0.15, -2.15±0.06, and -2.59±0.48, respectively) in pathological RBCs. The results were validated by western blotting and immunofluorescence microscopy. In addition, beta-actin from RTT patients also showed a dramatic increase in oxidative posttranslational modifications (PTMs) as the result of its binding with the lipid peroxidation product 4-hydroxy-2-nonenal (4-HNE). Our findings demonstrate, for the first time, a beta-actin down-regulation and oxidative PTMs for RBCs of RTT patients, thus indicating an altered cytoskeletal organization.
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy; Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Cortelazzo
authors.affiliation: Neonatal Intensive Care Unit, University Hospital, AOUS, Siena, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: De Felice
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pecorelli
authors.affiliation: Department of Medical Sciences Surgical and Neuroscience, University Hospital, AOUS, Siena, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Belmonte
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Signorini
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Leoncini
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy; Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Gloria
authors.initials: G
authors.lastname: Zollo
authors.affiliation: Department of Life Science, University of Siena, Siena, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Capone
authors.affiliation: Department of Life Science, University of Siena, Siena, Italy.
authors.forename: Cinzia Della
authors.initials: CD
authors.lastname: Giovampaola
authors.affiliation: Department of Sciences of Life and Biotechnologies, University of Ferrara, Ferrara, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sticozzi
authors.affiliation: Department of Sciences of Life and Biotechnologies, University of Ferrara, Ferrara, Italy; Department of Food and Nutrition, Kyung Hee University, Seoul, South Korea.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Valacchi
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Ciccoli
authors.affiliation: Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Guerranti
authors.affiliation: Child Neuropsychiatry Unit, University Hospital, Azienda Ospedaliera Universitaria Senese (AOUS), Siena, Italy.
authors.forename: Joussef
authors.initials: J
authors.lastname: Hayek
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000172:deficiency*; D000447:Aldehydes / Q000378:metabolism; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D015227:Lipid Peroxidation; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015518:Rett Syndrome / Q000378:metabolism* / Q000473:pathology
chemical_list: D000199:Actins; D000447:Aldehydes; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D020033:Protein Isoforms; C027576:4-hydroxy-2-nonenal