Synaptosomal Proteome of the Orbitofrontal Cortex from Schizophrenia Patients Using Quantitative Label-Free and iTRAQ-Based Shotgun Proteomics

Author(s)

Velasquez, Erika ^[1] ; Nogueira, Fabio C. S. ^{[1, 2]} ; Velasquez, Ingrid ^[3] ; Schrnitt, Andrea ^[4] ; Falkai, Peter ^[4] ; Domont, Gilberto B. ^[1] ; Martins-de-Souza, Daniel ^{[5, 6, 7]}

Affiliation

^[1] Univ Fed Rio de Janeiro, Inst Chem, Dept Biochem, Prote Unit, BR-21941909 Rio De Janeiro, RJ - Brazil

^[2] Univ Fed Rio de Janeiro, Inst Chem, LADETEC, Lab Prote, BR-21941598 Rio De Janeiro, RJ - Brazil

^[3] Univ Carabobo, Naguanagua 2005, Carabobo - Venezuela

^[4] Ludwig Maximilian Univ Munich LMU, Dept Psychiat & Psychotherapy, D-80336 Munich - Germany

^[5] Univ Estadual Campinas, Inst Biol, Dept Biochem, Lab Neuroprote, BR-13083862 Campinas, SP - Brazil

^[6] Univ Estadual Campinas, Neurobiol Ctr, BR-13083888 Campinas, SP - Brazil

^[7] Conselho Nacl Desenvolvimento Cient & Tecnol, Inst Nacl Biomarcadores Neuropsiquiatria INBION, BR-01060970 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PROTEOME RESEARCH; v. 16, n. 12, p. 4481-4494, DEC 2017.
• Web of Science Citations: 8

Abstract

Schizophrenia is a chronic and incurable neuropsychiatric disorder that affects about one percent of the world population. The proteomic characterization of the synaptosome fraction of the orbitofrontal cortex is useful for providing valuable information about the molecular mechanisms of synaptic functions in these patients. Quantitative analyses of synaptic proteins were made with eight paranoid schizophrenia patients and a pool of eight healthy controls free of mental diseases. Label-free and iTRAQ labeling identified a total of 2018 protein groups. Statistical analyses revealed 12 and 55 significantly dysregulated proteins by iTRAQ and label-free, respectively. Quantitative proteome analyses showed an imbalance in the calcium signaling pathway and proteins such as reticulon-1 and cytochrome c, related to endoplasmic reticulum stress and programmed cell death. Also, it was found that there is a significant increase in limbic-system-associated membrane protein and alpha-calcium/calmodulin-dependent protein kinase II, associated with the regulation of human behavior. Our data contribute to a better understanding about apoptosis as a possible pathophysiological mechanism of this disease as well as neural systems supporting social behavior in schizophrenia. This study also is a joint effort of the Chr 15 C-HPP team and the Human Brain Proteome Project of B/D-HPP. All MS proteomics data are deposited in the ProteomeXchange Repository under PXD006798. (AU)

• FAPESP's process: 14/10068-4 - Multi-User Equipment approved in grant 13/08711-3: mass spectrometer waters SYNAPT G2-Si HDMS + nanoACQUITY UPLC
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 13/08711-3 - Developing a predictive test for a successful medication response and understanding the molecular bases of schizophrenia through proteomics
• Grantee: Daniel Martins-de-Souza
• Support Opportunities: Research Grants - Young Investigators Grants