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Quantitative Subcellular Proteomics of the Orbitofrontal Cortex of Schizophrenia Patients.
- Source :
-
Journal of proteome research [J Proteome Res] 2019 Dec 06; Vol. 18 (12), pp. 4240-4253. Date of Electronic Publication: 2019 Oct 28. - Publication Year :
- 2019
-
Abstract
- 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 schizophrenia patients and 8 healthy controls identified 655 protein groups in the 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 protein 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. All MS data are available in the ProteomeXchange Repository under the identifier PXD015356 and PXD014350.
- Subjects :
- Adult
Aged
Aged, 80 and over
Case-Control Studies
Cell Nucleus metabolism
Cytoplasm metabolism
Female
Humans
Male
Mass Spectrometry
Membrane Proteins metabolism
Middle Aged
Mitochondria metabolism
Mitochondrial Proteins metabolism
NF-kappa B metabolism
Prefrontal Cortex chemistry
Proteomics methods
Voltage-Dependent Anion Channel 1 metabolism
Prefrontal Cortex cytology
Prefrontal Cortex metabolism
Schizophrenia metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1535-3907
- Volume :
- 18
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of proteome research
- Publication Type :
- Academic Journal
- Accession number :
- 31581776
- Full Text :
- https://doi.org/10.1021/acs.jproteome.9b00398