Dataset Information

QUANTITATIVE SUBCELLULAR PROTEOMICS OF THE ORBITOFRONTAL CORTEX OF SCHIZOPHRENIA PATIENTS

ABSTRACT: Schizophrenia is a chronic disease characterized by the impairment of mental functions with a marked social dysfunction. A proteomic approach using iTRAQ labeling and selected reaction monitoring, applied to the characterization of mitochondria (MIT), crude nuclear fraction (NUC) and cytoplasm (CYT), can allow the observation of dynamic changes in cell compartments providing valuable insights concerning schizophrenia physiopathology. Mass spectrometry analyses of the orbitofrontal cortex from 12 schizophrenia patients and 8 healthy controls identified 655 protein groups in MIT fraction, 1500 in NUC and 1591 in CYT. We found 166 groups of proteins dysregulated among all enriched cellular fractions. Through the quantitative proteomic analysis, we detect as the main biological pathways those related to calcium and glutamate imbalance, cell signaling disruption of CREB activation, axon guidance and proteins involved in the activation of NF-kB signaling along with the increase of complement proteins C3. Based on our data analysis, we suggest the activation of NF-kB as a possible pathway that links the deregulation of glutamate, calcium, apoptosis and the activation of the immune system in schizophrenia patients

INSTRUMENT(S): LTQ Orbitrap Velos, Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Brain

DISEASE(S): Schizophrenia

SUBMITTER: Proteomics Unit

LAB HEAD: Fabio nogueira

PROVIDER: PXD015356 | Pride | 2019-10-07

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Mito_20190807_iTRAQ-02.pdResult	Other
	Nucleo_iTRAQ_20190807-02.pdResult	Other
	VL_0000628_G1_MIT_REP1.raw	Raw
	VL_0000630_G1_MIT_REP2.raw	Raw
	VL_0000632_G1_MIT_REP3.raw	Raw

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Publications

Quantitative Subcellular Proteomics of the Orbitofrontal Cortex of Schizophrenia Patients.

Velásquez Erika E Martins-de-Souza Daniel D Velásquez Ingrid I Carneiro Gabriel Reis Alves GRA Schmitt Andrea A Falkai Peter P Domont Gilberto B GB Nogueira Fabio C S FCS

Journal of proteome research 20191028 12

Schizophrenia is a chronic disease characterized by the impairment of mental functions with a marked social dysfunction. A quantitative proteomic approach using iTRAQ labeling and SRM, applied to the characterization of mitochondria (MIT), crude nuclear fraction (NUC), and cytoplasm (CYT), can allow the observation of dynamic changes in cell compartments providing valuable insights concerning schizophrenia physiopathology. Mass spectrometry analyses of the orbitofrontal cortex from 12 schizophre ...[more]

PMID: 31581776

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Project description:Epigenetics describes mechanisms via which the environment can act on the genome, including DNA methylation of promoter regions of genes. This could be a way that environmental risk factors could affect neurodevelopment in individuals at risk for schizophrenia. Patient-derived cells provide a means whereby epigenetics and gene-environment interactions might be investigated. Induced pluripotent stem cells (iPS cells) present an attractive patient-derived cellular model because they can be differentiated into cell types of interest in schizophrenia. In this study the influence of the reprogramming process on schizophrenia-associated DNA methylation was investigated through genome-wide DNA methylation profiling and gene expression of patient-derived iPS cells and the fibroblasts from which they were derived. Olfactory neurosphere-derived cells (ONS cells) from the same patients were also profiled to provide a window on epigenetic regulation in three distinct cell types. Patient-derived cell were compared to cells derived from healthy controls to identify differences in DNA methylation and gene expression associated with schizophrenia in three cell types. The main finding is that iPS cells, prior to neuronal differentiation, demonstrated significant schizophrenia-associated differences in DNA methylation. This is in contrast to the fibroblasts from which they were derived, which show lesser schizophrenia-associated differences in DNA methylation. Like iPS cells, ONS cells showed robust significant schizophrenia-associated differences in DNA methylation. Notably, the schizophrenia-associated differences in DNA methylation were unique for each cell type, with little overlap between them, and only 5 genes commonly methylated in all cell types. Gene expression differences among the cell types mirrored the DNA methylation differences in magnitude, again with little overlap in specific genes affected. Gene Ontology analysis of the affected genes identified common cellular process affected in all three cell types without the same genes contributing. These data suggest that most DNA methylation differences are driven by the demands imposed by each cell type with schizophrenia-associated differences also being cell-type specific. Thus DNA methylation may not be a cause of schizophrenia-associated differences in cell functions in these cells but rather a downstream consequence of some unidentified causative mechanisms. This dataset represents the DNA methylation part of the study. The gene expression data is deposited under accession E-MTAB-5016.