Mass spectrometry identification of potential biomarker proteins in the 150-kD electrophoretic band in patients with schizophrenia

Abstract

Background:Diagnosing schizophrenia is primarily based on the presentation of defined signs and symptoms, none of which is pathognomonic for this group of syndromes. However, few significant genome-wide associations between schizophrenia and individual have detected. Protein profiling of candidate serum biomarkers in schizophrenia is therefore an area of great interest.Methods:In the present study, we used a combination of 7% polyethylene glycol (PEG) enrichment of immune complexes and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to separate abnormal band, then analyse the band with liquid chromatography mass spectrometry (LC-MS).Results:There is a special 150-kD electrophoretic band in patients with schizophrenia, bipolar disorder, or depression relative to healthy controls (each 30 samples). Analysis of the band using LC-MS resulted in the identification of 11 serum proteins whose abundance was altered between patients and controls. Among them, 8 proteins (CFH, CFB, cDNA FLJ75416, zinc finger protein 729, isoform 2 of nidogen-1, diaphanous-1, cDNA FLJ77762, and cDNA FLJ58411) were up regulated, while one protein (isoform 1 of collagen alpha-1 (II) was down regulated in patients with schizophrenia, but only zinc finger protein 729 has statistics significance (P < .05). No differences were noted with regard to thrombospondin-1 or collagen alpha-2 (I) among the 3 groups. These proteins take part in several biological functions such as focal adhesion, complement cascades, ECM-receptor interaction, and Staphylococcus aureus infection.Conclusions:The 150-kD electrophoretic band or zinc finger protein 729 may become biomarkers in patients with schizophrenia. In the future increasing sample size and function research of zinc finger protein 729 should be executed continuously.

FN1, Collagen, MMP-2, and Lumican Associated with ECM Organization with Multiple Signaling Pathways Dysfunction in Schizophrenia Pathogenesis by Network Biology Approaches

“…Evidence reported that the collagen chain gene (COL1A1) expression might be associated with the EMC ligands, thus resulting in the inactivation of DDR1 with a timedependent decrease in the SZ patients 58 . In addition, evidence reported that COL1A1 and COL1A2 genes expression levels were signi cantly decreased in patients with SZ compared to control 59 . One of the most increased genes, COL3A1, is detected, which encodes the pro-1 chains of type III collagen and exhibits a de novo mutation in SZ patients 60 .…”

The Role of Brain Microvascular Endothelial Cell and Blood-Brain Barrier Dysfunction in Schizophrenia

“…In other postmortem studies, a reduced brain expression of LAMA1, FN1, COL4A1, and COL4A2 has been previously reported in schizophrenia [12]. In a serum proteomic analysis of paranoid schizophrenia patients, researchers found reductions in COL4A1 but not COL4A2, although this effect was not significant [106]. De novo mutations have been identified in schizophrenia for LAMA1 (missense mutation) [87] and LAMA2 (frameshift and splice site mutations) [107].…”

Biomarkers in Psychiatry: Concept, Definition, Types and Relevance to the Clinical Reality

“…These proteins have been proposed as biomarker candidates for prognosis, diagnosis, and medication monitoring in SCZ (72,73). One of these proteins is zinc finger protein 729 that was found significantly downregulated in patients with SCZ compared to healthy individuals and patients diagnosed with depression or BD (74). Another example is the study that showed reduced plasma levels of glia maturation factor beta (GMF-b), the brain-derived neurotrophic factor (BDNF), and the 115-kDa isoform of the Rab3 GTPaseactivating protein catalytic subunit (RAB3GAP1) in SCZ patients.…”