Quantitative Subcellular Proteomics of the Orbitofrontal Cortex of Schizophrenia Patients

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.