Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children
Chiara Lanzillotta,
Viviana Greco,
Diletta Valentini,
Alberto Villani,
Valentina Folgiero,
Matteo Caforio,
Franco Locatelli,
Sara Pagnotta,
Eugenio Barone,
Andrea Urbani,
Fabio Di Domenico,
Marzia Perluigi
Affiliations
Chiara Lanzillotta
Department of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Viviana Greco
Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Diletta Valentini
Pediatric and Infectious Disease Unit, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Alberto Villani
Pediatric and Infectious Disease Unit, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Valentina Folgiero
Department of Pediatric Hematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Matteo Caforio
Department of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Franco Locatelli
Department of Pediatric Hematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children’s Hospital, 00165 Rome, Italy
Sara Pagnotta
Department of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Eugenio Barone
Department of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Andrea Urbani
Department of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Fabio Di Domenico
Department of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Marzia Perluigi
Department of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, Italy
Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. To search for biomarkers for the early detection and exploration of the disease mechanisms, here, we investigated the protein expression signature of peripheral blood mononuclear cells (PBMCs) in DS children compared with healthy donors (HD) by using an in-depth label-free shotgun proteomics approach. Identified proteins are found associated with metabolic pathways, cellular trafficking, DNA structure, stress response, cytoskeleton network, and signaling pathways. The results showed that a well-defined number of dysregulated pathways retain a prominent role in mediating DS pathological features. Further, proteomics results are consistent with published study in DS and provide evidences that increased oxidative stress and the increased induction of stress related response, is a participant in DS pathology. In addition, the expression levels of some key proteins have been validated by Western blot analysis while protein carbonylation, as marker of protein oxidation, was investigated. The results of this study propose that PBMCs from DS children might be in an activated state where endoplasmic reticulum stress and increased production of radical species are one of the primary events contributing to multiple DS pathological features.
