Abnormalities of the anterior cingulate cortex have previously been described in schizophrenia, major depressive disorder and bipolar disorder. In this study 2-DE was performed followed by mass spectrometric sequencing to identify disease-specific protein changes within the anterior cingulate cortex in these psychiatric disorders. The 2-DE system comprised IPGs 4-7 and 6-9 in the first, IEF dimension and SDS-PAGE in the second dimension. Resultant protein spots were compared between control and disease groups. Statistical analysis indicated that 35 spots were differentially expressed in one or more groups. Proteins comprising 26 of these spots were identified by mass spectroscopy. These represented 19 distinct proteins; aconitate hydratase, malate dehydrogenase, fructose bisphosphate aldolase A, ATP synthase, succinyl CoA ketoacid transferase, carbonic anhydrase, alpha- and beta-tubulin, dihydropyrimidinase-related protein-1 and -2, neuronal protein 25, trypsin precursor, glutamate dehydrogenase, glutamine synthetase, sorcin, vacuolar ATPase, creatine kinase, albumin and guanine nucleotide binding protein beta subunit. All but three of these proteins have previously been associated with the major psychiatric disorders. These findings provide support for the view that cytoskeletal and mitochondrial dysfunction are important components of the neuropathology of the major psychiatric disorders.

There is evidence for both similarity and distinction in the presentation and molecular characterization of schizophrenia and bipolar disorder. In this study, we characterized protein abnormalities in the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder using two-dimensional gel electrophoresis. Tissue samples were obtained from 35 individuals with schizophrenia, 35 with bipolar disorder and 35 controls. Eleven protein spots in schizophrenia and 48 in bipolar disorder were found to be differentially expressed (P < 0.01) in comparison to controls, with 7 additional spots found to be altered in both diseases. Using mass spectrometry, 15 schizophrenia-associated proteins and 51 bipolar disorder-associated proteins were identified. The functional groups most affected included synaptic proteins (7 of the 15) in schizophrenia and metabolic or mitochondrial-associated proteins (25 of the 51) in bipolar disorder. Six of seven synaptic-associated proteins abnormally expressed in bipolar disorder were isoforms of the septin family, while two septin protein spots were also significantly differentially expressed in schizophrenia. This finding represented the largest number of abnormalities from one protein family. All septin protein spots were upregulated in disease in comparison to controls. This study provides further characterization of the synaptic pathology present in schizophrenia and of the metabolic dysfunction observed in bipolar disorder. In addition, our study has provided strong evidence implicating the septin protein family of proteins in psychiatric disorders for the first time.

No abstract

Proteomic technologies, such as yeast twohybrid, mass spectrometry (MS), protein/peptide arrays and fluorescence microscopy, yield multi-dimensional data sets, which are often quite large and either not published or published as supplementary information that is not easily searchable. Without a system in place for standardizing and sharing data, it is not fruitful for the biomedical community to contribute these types of data to centralized repositories. Even more difficult is the annotation and display of pertinent information in the context of the corresponding proteins. Wikipedia, an online encyclopedia that anyone can edit, has already proven quite successful1 and can be used as a model for sharing biological data. However, the need for experimental evidence, data standardization and ownership of data creates scientific obstacles. Here, we describe Human Proteinpedia (http://www.humanproteinpedia.org/) as a portal that overcomes many of these obstacles to provide an integrated view of the human proteome. Human Proteinpedia also allows users to contribute and edit proteomic data with two significant differences from Wikipedia: first, the contributor is expected to provide experimental evidence for the data annotated; and second, only the original contributor can edit their data. Human Proteinpedia's annotation system provides investigators with multiple options for contributing data including web forms and annotation servers. Although registration is required to contribute data, anyone can freely access the data in the repository. The web forms simplify submission through the use of pull-down menus for certain data fields and pop-up menus for standardized vocabulary terms. Distributed annotation servers using modified protein DAS (distributed annotation system) protocols developed by us (DAS protocols were originally developed for sharing mRNA and DNA data) permit contributing laboratories to maintain protein annotations locally. All protein annotations are visualized in the context of corresponding proteins in the Human Protein Reference Database (HPRD)3. Figure 1 shows tissue expression data for alpha-2-HS glycoprotein derived from three different types of experiments. Our unique effort differs significantly from existing repositories, such as PeptideAtlas and PRIDE5 in several respects. First, most proteomic repositories are restricted to one or two experimental platforms, whereas Human Proteinpedia can accommodate data from diverse platforms, including yeast two-hybrid screens, MS, peptide/protein arrays, immunohistochemistry, western blots, coimmunoprecipitation and fluorescence microscopy-type experiments. Second, Human Proteinpedia allows contributing laboratories to annotate data pertaining to six features of proteins (posttranslational modifications, tissue expression, cell line expression, subcellular localization, enzyme substrates and protein-protein interactions;). No existing repository currently permits annotation of all these features in proteins. Third, all data submitted to Human Proteinpedia...