A5075757387- Peptidase Inhibition and Analysis
- Neuropeptides and Animal Physiology
- Ubiquitin and proteasome pathways
- Protein Hydrolysis and Bioactive Peptides
- Signaling Pathways in Disease
- Receptor Mechanisms and Signaling
- Glycosylation and Glycoproteins Research
- Cannabis and Cannabinoid Research
- Antimicrobial Peptides and Activities
- Neuroscience and Neuropharmacology Research
- Sleep and Wakefulness Research
- Protease and Inhibitor Mechanisms
- Venomous Animal Envenomation and Studies
- Advanced Proteomics Techniques and Applications
- Biochemical effects in animals
- Biochemical and Structural Characterization
- Chemical Synthesis and Analysis
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Adipose Tissue and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Adenosine and Purinergic Signaling
- Endoplasmic Reticulum Stress and Disease
- Neuroendocrine regulation and behavior
- Pancreatic function and diabetes
- Neuroscience of respiration and sleep
Universidade de São Paulo
2015-2024
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
2023
Weizmann Institute of Science
2020-2022
Institute of Biomedical Science
2003-2019
Instituto Biológico
2019
International Institute of Tropical Agriculture
2009
Icahn School of Medicine at Mount Sinai
1999-2006
Universidade Estadual de Campinas (UNICAMP)
2004
Instituto Butantan
2001
Universidade Federal de São Paulo
2001
Leptospira species colonize a significant proportion of rodent populations worldwide and produce life-threatening infections in accidental hosts, including humans. Complete genome sequencing interrogans serovar Copenhageni comparative analysis with the available Lai reveal that despite overall genetic similarity there are structural differences, large chromosomal inversion extensive variation number distribution insertion sequence elements. Genome elucidates many novel aspects leptospiral...
Xylella fastidiosa is a xylem-dwelling, insect-transmitted, gamma-proteobacterium that causes diseases in many plants, including grapevine, citrus, periwinkle, almond, oleander, and coffee. X. has an unusually broad host range, extensive geographical distribution throughout the American continent, induces diverse disease phenotypes. Previous molecular analyses indicated three distinct groups of isolates were expected to be genetically divergent. Here we report genome sequence (Temecula...
To date, the endogenous ligands described for cannabinoid receptors have been derived from membrane lipids. identify a peptide ligand CB(1) receptors, we used recently conformation-state sensitive antibodies and screened panel of peptides rodent brain or adipose tissue. This led to identification hemopressin (PVNFKFLSH) as that selectively binds receptors. We find is receptor-selective antagonist, because it able efficiently block signaling by but not other members family A G protein-coupled...
Hemopressin (Hp), a 9-residue α-hemoglobin-derived peptide, was previously reported to function as CB1 cannabinoid receptor antagonist (1). In this study, we report that mass spectrometry (MS) data from peptidomics analyses of mouse brain extracts identified N-terminally extended forms Hp containing either three (RVD-Hpa) or two (VD-Hpa) additional amino acids, well β-hemoglobin-derived peptide with sequence similarity hemopressin (VD-Hpβ). Characterization the peptides using binding and...
Endopeptidase 24.15 (EC; ep24.15), neurolysin ep24.16), and angiotensin-converting enzyme ACE) are metallopeptidases involved in neuropeptide metabolism vertebrates. Using catalytically inactive forms of ep24.15 ep24.16, we have identified new peptide substrates for these enzymes. The enzymatic activity ep24.16 was inactivated by site-directed mutagenesis amino acid residues within their conserved HEXXH motifs, without disturbing secondary structure or binding ability, as shown circular...
The genome sequence of Leifsonia xyli subsp. xyli, which causes ratoon stunting disease and affects sugarcane worldwide, was determined. single circular chromosome CTCB07 2.6 Mb in length with a GC content 68% 2,044 predicted open reading frames. analysis also revealed 307 pseudogenes, is more than any bacterial plant pathogen sequenced to date. Many these if functional, would likely be involved the degradation heteropolysaccharides, uptake free sugars, synthesis amino acids. Although L. has...
Protein degradation by the ubiquitin proteasome system releases large amounts of oligopeptides within cells. To investigate possible functions for these intracellularly generated oligopeptides, we fused them to a cationic transactivator peptide sequence using reversible disulfide bonds, introduced into cells, and analyzed their effect on G protein-coupled receptor (GPCR) signal transduction. A mixture containing four peptides (20-80 microm) significantly inhibited increase in extracellular...
Bortezomib is an antitumor drug that competitively inhibits proteasome beta-1 and beta-5 subunits. While the impact of bortezomib on protein stability known, effect this intracellular peptides has not been previously explored. A quantitative peptidomics technique was used to examine treating human embryonic kidney 293T (HEK293T) cells with 5–500 nM for various lengths time (30 minutes 16 hours), neuroblastoma SH-SY5Y 500 1 hour. Although treatment decreased levels some peptides, majority...
A growing body of evidence indicates that G-protein-coupled receptors undergo complex conformational changes upon agonist activation. It is likely the extracellular region, including N terminus, undergoes activation-dependent changes. We examined this by generating antibodies to regions within terminus micro-opioid receptors. find midportion N-terminal tail exhibit enhanced recognition activated receptors, whereas those distal do not. The abolished treatment with agents block G-protein...
Thimet oligopeptidase (EC 3.4.24.15; EP24.15) is an intracellular enzyme that has been proposed to metabolize peptides within cells, thereby affecting antigen presentation and G protein-coupled receptor signal transduction. However, only a small number of substrates EP24.15 have reported previously. Here we identified over 100 in human embryonic kidney 293 (HEK293) cells are derived from proteins; many but not all these or products EP24.15. First, cellular were extracted HEK293 incubated...
Peptides have been proposed to function in intracellular signaling within the cytosol. Although cytosolic peptides are considered be highly unstable, a large number of detected mouse brain and other biological samples. In present study, we evaluated peptidome three diverse cell lines: SH-SY5Y, MCF7, HEK293 cells. A comparison peptidomes revealed considerable overlap identity found each line. The majority observed not derived from most abundant or least stable proteins cell, approximately...
Peptides derived from cytosolic, mitochondrial, and nuclear proteins have been detected in extracts of animal tissues cell lines. To test whether the proteasome is involved their formation, HEK293T cells were treated with epoxomicin (0.2 or 2 μM) for 1 h quantitative peptidomics analysis was performed. Altogether, 147 unique peptides identified by mass spectrometry sequence analysis. Epoxomicin treatment decreased levels majority intracellular peptides, consistent inhibition beta-2 beta-5...
The proteasome cleaves intracellular proteins into peptides. Earlier studies found that treatment of human embryonic kidney 293T (HEK293T) cells with epoxomicin (an irreversible inhibitor) generally caused a decrease in levels However, bortezomib antitumor drug and an unexpected increase the most peptides HEK293T SH-SY5Y cells. To address this apparent paradox, quantitative peptidomics was used to study effect variety other inhibitors on peptide Inhibitors tested included carfilzomib, MG132,...
Peptidomics techniques have identified hundreds of peptides that are derived from proteins present mainly in the cytosol, mitochondria, and/or nucleus; these termed intracellular to distinguish them secretory pathway function primarily outside cell. The proteasome and thimet oligopeptidase participate production metabolism peptides. Many common among mouse tissues human cell lines analyzed likely perform a variety functions within cells. Demonstrated include modulation signal transduction,...
Peptides function as signaling molecules in species diverse humans and yeast. Mass spectrometry-based peptidomics techniques provide a relatively unbiased method to assess the peptidome of biological samples. In present study, we used quantitative peptidomic technique characterize yeast Saccharomyces cerevisiae compare it peptidomes mammalian cell lines tissues. Altogether, 297 peptides derived from 75 proteins were identified. The are similar those human average size amino acid composition....
Abstract Background Cachexia is a paraneoplastic syndrome related with poor prognosis. The tumour micro‐environment contributes to systemic inflammation and increased oxidative stress as well fibrosis. aim of the present study was characterise inflammatory circulating factors profile, potentially contributing fibrosis in cachectic cancer patients. Methods 74 patients (weight stable n = 31; 43) diagnosed colorectal were recruited, biopsies collected during surgery. Multiplex assay performed...
We report a systematic and detailed analysis of recombinant neurolysin (EC 3.4.24.16) specificity in parallel with thimet oligopeptidase (TOP, EC 3.4.24.15) using Bk sequence its C- N-terminal extensions as human kininogen motif for synthesis internally quenched fluorescent substrates. The influence the substrate size was investigated, longest peptide susceptible to TOP contains 17 amino acids. specificities both oligopeptidases sites P4 P3' were also characterized great detail seven series...
J. Neurochem. (2010) 113 , 871–880. Abstract Many hemoglobin‐derived peptides are present in mouse brain, and several of these have bioactive properties including the hemopressins, a related series that bind to cannabinoid CB1 receptors. Although hemoglobin is major component red blood cells, it also neurons glia. To examine whether brain similar those heart, we used peptidomics approach involving mass spectrometry. found only not blood, whereas all heart were seen blood. Thus, likely...
Purkinje cell degeneration (pcd) mice have a mutation within the gene encoding cytosolic carboxypeptidase 1 (CCP1/Nna1), which has homology to metallocarboxypeptidases. To assess function of CCP1/Nna1, quantitative proteomics and peptidomics approaches were used compare proteins peptides in mutant wild-type mice. Hundreds derived from mitochondrial are greatly elevated pcd mouse hypothalamus, amygdala, cortex, prefrontal striatum. However, major detected on 2-D gel electrophoresis present...
Intracellular peptides generated by the proteasome and oligopeptidases have been suggested to function in signal transduction improve insulin resistance mice fed a high‐caloric diet. The aim of this study was identify specific intracellular adipose tissue Wistar rats that could be associated with physiological therapeutic control glucose uptake. Using semiquantitative mass spectrometry LC/MS/MS analyses, we identified ten epididymal rats; three these were present at increased levels Western...
The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate the catabolism of bioactive peptides such as neurotensin bradykinin. Recently, it suggested that Nln reduction could improve insulin sensitivity. Here, we have KO mice increased glucose tolerance, sensitivity, gluconeogenesis. liver mRNA for several genes related Isotopic label semiquantitative peptidomic analysis suggests an increase specific...