Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children
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 p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/11/1112 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chiara Lanzillotta |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T14:55:49Z |
| format | Article |
| id | doaj.art-6224f133e6ca4eb680e6e33981f078d7 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T14:55:49Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-6224f133e6ca4eb680e6e33981f078d72023-11-20T20:35:15ZengMDPI AGAntioxidants2076-39212020-11-01911111210.3390/antiox9111112Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome ChildrenChiara Lanzillotta0Viviana Greco1Diletta Valentini2Alberto Villani3Valentina Folgiero4Matteo Caforio5Franco Locatelli6Sara Pagnotta7Eugenio Barone8Andrea Urbani9Fabio Di Domenico10Marzia Perluigi11Department of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyPediatric and Infectious Disease Unit, Bambino Gesù Children’s Hospital, 00165 Rome, ItalyPediatric and Infectious Disease Unit, Bambino Gesù Children’s Hospital, 00165 Rome, ItalyDepartment of Pediatric Hematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children’s Hospital, 00165 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Pediatric Hematology/Oncology and of Cell and Gene Therapy, Bambino Gesù Children’s Hospital, 00165 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Basic Biotechnological Sciences, Intensivological and Perioperative Clinics, Università Cattolica del Sacro Cuore, 00168 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Biochemical Sciences “A. Rossi Fanelli”, Laboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, 00185 Rome, ItalyDown 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.https://www.mdpi.com/2076-3921/9/11/1112proteomicsDown syndromeperipheral blood mononuclear cells (PBMCs)unfolded protein responseoxidative stress |
| spellingShingle | 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 Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children Antioxidants proteomics Down syndrome peripheral blood mononuclear cells (PBMCs) unfolded protein response oxidative stress |
| title | Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children |
| title_full | Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children |
| title_fullStr | Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children |
| title_full_unstemmed | Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children |
| title_short | Proteomics Study of Peripheral Blood Mononuclear Cells in Down Syndrome Children |
| title_sort | proteomics study of peripheral blood mononuclear cells in down syndrome children |
| topic | proteomics Down syndrome peripheral blood mononuclear cells (PBMCs) unfolded protein response oxidative stress |
| url | https://www.mdpi.com/2076-3921/9/11/1112 |
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