Peptidomic analysis of the anterior temporal lobe and corpus callosum from schizophrenia patients

Café-Mendes, Cecilia C.; Ferro, Emer S.; Torrão, Andréa da Silva; Crunfli, Fernanda; Rioli, Vanessa; Schmitt, Andrea; Falkai, Peter; Britto, Luiz R.G.; Turck, Christoph W.; Martins-de-Souza, Daniel

doi:10.1016/j.jprot.2016.05.025

Cited by 24 publications

(19 citation statements)

References 61 publications

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“…Literature data have shown that although several hundreds of intracellular peptides have been identified in the brain, the functional characterization of only a few sequences have been investigated. 23,24,26,27,[45][46][47][48][49] Among the peptides identified herein that have been previously shown to have pharmacological activity is TVGDVNTARPGMLDF. This peptide belongs to a family of peptides commonly known as diazepam binding inhibitor (DBI), which have been previously described to have multiple actions in the brain and in peripheral tissues.…”

Section: Discussionmentioning

confidence: 90%

Characterization of Intracellular Peptides from Zebrafish (Danio rerio) Brain

et al. 2019

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Peptides represent a large class of cell signaling molecules, and they are mainly produced by the classical secretory pathway or during protein degradation. The peptide profile of Danio rerio (zebrafish) shows a lack of information when compared with other consolidated animal models. The aim of this work was to characterize the peptide profile of zebrafish brain by using triplex reductive methylation of amines labeling and liquid chromatography coupled to electron spray mass spectrometry. A total of 411 peptide fragments were detected and 125 peptide sequences could be solved. Further analysis suggested that most of the peptides were fragments of intracellular cytosolic and mitochondrial proteins, and that 60% of the precursor proteins were cleaved at either their Nor C-terminal. The most common residue in the P1 position was leucine whereas other common residues were lysine, alanine, arginine, and phenylalanine. Rare cleavage sites at P1 position were histidine, glutamic acid, and isoleucine. The peptide profile of zebrafish brain has similarities with results previously described in mice brain peptidome studies. Thus, this study represents an important basis for the molecular understanding of zebrafish and its use as a model for human diseases.

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Section: Discussionmentioning

confidence: 90%

Characterization of Intracellular Peptides from Zebrafish (Danio rerio) Brain

et al. 2019

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“…Intracellular peptides containing putative post-translational modification sites were previously shown to modulate protein kinase and peptidase activities [10,70]. The histone-derived intracellular peptides that were identified to be differentially expressed in the brains of schizophrenic patients were also shown to be neuroprotective [14]. The expression of non-specific lipid-transfer protein, also known as sterol carrier protein (2SCP-2), significantly altered the association of several proteins (important to lipid droplet metabolism) with purified lipid droplets both in vitro as well as in intact cells [101].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, our group developed a substrate-capture assay using a catalytically inactive form of thimet oligopeptidase (EC 3.4.24.15, EP24.15; THOP1) that allowed for the seminal identification of mammalian intracellular peptides, which are products of proteasome activity distinct from MHC-I antigens [9,10]. To date, multiple research groups have identified hundreds of novel intracellular peptides in human cell lines [11,12], human tissues [13,14], rodents [15,16], zebrafish [17], yeast [18], and plants [19,20]. THOP1 only hydrolyzes a restricted group of peptides in the optimal range of 8-12 amino acids in length [21][22][23], and has never been shown to degrade proteins, likely due to its catalytic site being deeply located in the bottom of a narrow channel [24,25].…”

Section: Introductionmentioning

confidence: 99%

The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity

et al. 2020

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Thimet oligopeptidase (EC 3.4.24.15; EP24.15; THOP1) is a potential therapeutic target, as it plays key biological functions in processing biologically functional peptides. The structural conformation of THOP1 provides a unique restriction regarding substrate size, in that it only hydrolyzes peptides (optimally, those ranging from eight to 12 amino acids) and not proteins. The proteasome activity of hydrolyzing proteins releases a large number of intracellular peptides, providing THOP1 substrates within cells. The present study aimed to investigate the possible function of THOP1 in the development of diet-induced obesity (DIO) and insulin resistance by utilizing a murine model of hyperlipidic DIO with both C57BL6 wild-type (WT) and THOP1 null (THOP1−/−) mice. After 24 weeks of being fed a hyperlipidic diet (HD), THOP1−/− and WT mice ingested similar chow and calories; however, the THOP1−/− mice gained 75% less body weight and showed neither insulin resistance nor non-alcoholic fatty liver steatosis when compared to WT mice. THOP1−/− mice had increased adrenergic-stimulated adipose tissue lipolysis as well as a balanced level of expression of genes and microRNAs associated with energy metabolism, adipogenesis, or inflammation. Altogether, these differences converge to a healthy phenotype of THOP1−/− fed a HD. The molecular mechanism that links THOP1 to energy metabolism is suggested herein to involve intracellular peptides, of which the relative levels were identified to change in the adipose tissue of WT and THOP1−/− mice. Intracellular peptides were observed by molecular modeling to interact with both pre-miR-143 and pre-miR-222, suggesting a possible novel regulatory mechanism for gene expression. Therefore, we successfully demonstrated the previously anticipated relevance of THOP1 in energy metabolism regulation. It was suggested that intracellular peptides were responsible for mediating the phenotypic differences that are described herein by a yet unknown mechanism of action.

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“…Taken together, these data suggested for the first time that extra-lysosomal proteolysis by proteasomes and oligopeptidases could produce novel functional peptides, which may modulate protein interactions within cells [19]. Further studies using electron spray mass spectrometry and peptidomics techniques corroborated these initial findings, and thousands of novel intracellular peptides have now been identified in plants [20,21], yeast [22], zebrafish [23], rodents [24,25,26], human cell lines [27,28,29], and human tissues [30,31]. It is worth to mention that MHC proteins and immunoproteasomes emerge later in evolution than regular proteasomes [32].…”

Section: Intracellular Peptides—a Brief Historical Retrospectivementioning

confidence: 99%

“…PepH is an intracellular peptide identified in postmortem samples of schizophrenia (SCZ) patients [30]. Histone H2B type 1-H that gives rise to PepH is located in the 8-Mb xMHC region on chromosome 6 that contains over 250 protein-coding genes.…”

Section: Pharmacological and Biochemical Analyses Of Intracellularmentioning

confidence: 99%

Intracellular Peptides in Cell Biology and Pharmacology

et al. 2019

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Intracellular peptides are produced by proteasomes following degradation of nuclear, cytosolic, and mitochondrial proteins, and can be further processed by additional peptidases generating a larger pool of peptides within cells. Thousands of intracellular peptides have been sequenced in plants, yeast, zebrafish, rodents, and in human cells and tissues. Relative levels of intracellular peptides undergo changes in human diseases and also when cells are stimulated, corroborating their biological function. However, only a few intracellular peptides have been pharmacologically characterized and their biological significance and mechanism of action remains elusive. Here, some historical and general aspects on intracellular peptides’ biology and pharmacology are presented. Hemopressin and Pep19 are examples of intracellular peptides pharmacologically characterized as inverse agonists to cannabinoid type 1 G-protein coupled receptors (CB1R), and hemopressin fragment NFKF is shown herein to attenuate the symptoms of pilocarpine-induced epileptic seizures. Intracellular peptides EL28 (derived from proteasome 26S protease regulatory subunit 4; Rpt2), PepH (derived from Histone H2B type 1-H), and Pep5 (derived from G1/S-specific cyclin D2) are examples of peptides that function intracellularly. Intracellular peptides are suggested as biological functional molecules, and are also promising prototypes for new drug development.

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Peptidomic analysis of the anterior temporal lobe and corpus callosum from schizophrenia patients

Cited by 24 publications

References 61 publications

Characterization of Intracellular Peptides from Zebrafish (Danio rerio) Brain

Characterization of Intracellular Peptides from Zebrafish (Danio rerio) Brain

The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity

Intracellular Peptides in Cell Biology and Pharmacology

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