MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v05/MSV000091101/primary200OKProf. Oliver Schillinghttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=f263e3c8b6f54ff3a5685be546cbfb43oliver.schilling@mol-med.uni-freiburg.deMassIVE764UNIMOD:4 - "Iodoacetamide derivative."ProteomicsQ Exactive PlusMus Musculus (ncbitaxon:10090)Institute for Surgical Pathology, University Medical Center FreiburgSnakebite envenomation is classified as a Neglected Tropical Disease. Bothrops jararaca venom induces kidney injury and coagulopathy. HF3, a hemorrhagic metalloproteinase of B. jararaca venom, participates in the envenomation pathogenesis. We evaluated the effects of HF3 in mouse kidney and blood plasma after injection in the thigh muscle, mimicking a snakebite. Transcriptomic analysis showed differential expression of 31 and 137 genes related to kidney pathology after 2 h and 6 h, respectively. However, only subtle changes were observed in kidney proteome, with differential abundance of 15 proteins after 6 h, including kidney injury markers. N-terminomic analysis of kidney proteins showed 420 proteinase-generated peptides compatible with meprin specificity, indicating activation of host proteinases. Plasma analysis revealed differential abundance of 90 and 219 proteins, respectively, after 2 h and 6 h, including coagulation-cascade and complement-system components, and creatine-kinase, whereas a semi-specific search of N-terminal peptides indicated activation of endogenous proteinases. HF3 promoted host reactions, altering the gene expression and the proteolytic profile of kidney tissue, and inducing plasma proteome imbalance driven by changes in abundance and proteolysis. The overall response of the mouse underscores the systemic action of a hemorrhagic toxin that transcends local tissue damage and is related to known venom-induced systemic effects.Systemic toxicity of snake venom metalloproteinases: Multi-omics analyses of kidney and blood plasma disturbances in a mouse model.Trevisan-Silva Dilza D, Cosenza-Contreras Miguel M, Oliveira Ursula C UC, da Rós Nancy N, Andrade-Silva Débora D, Menezes Milene C MC, Oliveira Ana Karina AK, Rosa Jaqueline G JG, Sachetto Ana T A ATA, Biniossek Martin L ML, Pinter Niko N, Santoro Marcelo L ML, Nishiyama-Jr Milton Y MY, Schilling Oliver O, Serrano Solange M T SMTPlasma, Fresh, Mus musculus, Fresh Frozen Plasmas, Fresh Frozen, Laboratory Mice., Blood Plasma, portion of blood plasma, Frozen Plasma, Serpentes, Fresh Frozen Plasma, zootoxin, Peptidomics, Laboratory, Swiss, mice, Blood, Mus domesticus, mouse, Swiss Mouse, portion of plasma, House Mice, Swiss Mice, injury to kidney, Plasmas, kidney injury, kidney toxicity, House Mouse, domesticus, renal toxicity, Frozen Plasmas, blood plasm, Snake, House, Mus, Blood Plasmas, Ophidia, margin of safety, Mus musculus domesticus, toxic potential, Mouse, Venom, house mouse, Mice, Laboratory Mouse, plasmaFresh, Disorders, Fresh Frozen Plasma, determination, Peptidomics, Laboratory, Blood, regulation by symbiont of host system process, Mus domesticus, positive regulation by symbiont of host non-apoptotic programmed cell death, postpartum coagulation defect, Gene, upper leg muscle, Spectrum Analyses, Coagulation Disorder, House Mouse, Polypeptides, method, peptido, induction by organism of non-apoptotic programmed cell death in other organism during symbiotic interaction, House, Injection, method used in an experiment, Jararaca Venom, Coagulation Disorders, Mass, Gene Products, pathogenesis, Mus musculus domesticus, Analysis, envenomation resulting in modulation of process in other organism, Jaracetin, Mice, Injectables, Bothropoides jararaca, Mass Spectroscopy, Coagulopathy, Mass Spectrum Analysis, coagulation disorders, Fresh Frozen Plasmas, Fresh Frozen, thigh muscle, Blood Plasma, excessive bleeding, stimulation by symbiont of host programmed cell death, peptides, Analyses, Swiss, clotting disorder, Tissue, beta-Trypsin, Swiss Mice, labeling, causes, free, Jararhagin, Injectable, renal toxicity, envenomation resulting in modification of morphology or physiology of other organism, Disorder, blood, Blood Plasmas, envenomation resulting in modulation of process in another organism, causality, blood coagulation disorder, disorder, peptidos, Venom, Coagulation Defect, house mouse, plasma, thiol methyltransferase activity, reniculate kidney, close to, Bothrops jararaca, Frozen Plasma, Amine., activation by organism of non-apoptotic programmed cell death in other organism, hemolysin activity, Jararaca Snake, zootoxin, Proteins, disorders, mouse, envenomation, Plasmas, Spectrum Analysis, Peptide, near to, Spectroscopy, Frozen Plasmas, TPSG1, Blood Coagulation Disorder, S-adenosyl-L-methionine:thiol S-methyltransferase activity, MS, Mus, Protein, chemical analysis, proteomic analysis, modulation by symbiont of host system process, simple tissue, muscle of thigh, Mass Spectrum Analyses, blood coagulation disease, Plasma, Mus musculus, Mass Spectrum, portion of blood plasma, PRSS, coagulopathy, mice, coagulation defect, Tails, Swiss Mouse, Spectrometry, Tripcellim, Amine, portion of plasma, House Mice, injury to kidney, Blood Coagulation, study protocol, beta Trypsin, kidney injury, kidney toxicity, domesticus, Laboratory Mice, HF2 -Proteinase, Protein Gene Products, plan specification, Gene Proteins, Trypure, Kidneys, postpartum coagulation defect with delivery, blood plasm, blood coagulation, Snake, approaches, activation by symbiont of host programmed cell death, vicinity of, PRSS31, HF2 Proteinase, envenomation perturbing biological process, Peptid, Mouse, Polypeptide, assay, coagulation disorder, TMT, 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antigen, Esteroproteases, Polypeptides, Hydrolase, Generic Action, Lwr, Abnormal retropulsion test, peptido, diseases, Snake Envenoming, responsivity, Jararaca Venom, pathogenesis, diseases and disorders, Proteases, cytopathology, envenomation resulting in modulation of process in other organism, Injectables, Bothropoides jararaca, Coagulopathy, coagulation disorders, Fresh Frozen Plasmas, Fresh Frozen, human disease, Gene Expressions, stimulation by symbiont of host programmed cell death, peptides, ATP-dependent proteolysis, Glycine, Tissue, proteasome endopeptidase activity, Swiss Mice, ((amino(imino)methyl)(methyl)amino)acetic acid, Snakebite Envenomings, Proteolytic, Protein Degradation, Proteinases, N-amidinosarcosine, HCA1, blood, Pathologies, alpha-Methylguanidino acetic acid, Snake Envenomations, Homo sapiens disease, house mouse, plasma, N-(aminoiminomethyl)-N-methylglycine, reniculate kidney, Bothrops jararaca, Frozen Plasma, elastase activity, Proteinase, Degradations, 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coagulation disorder, disorder, peptidos, Hemolytic, Expression, Venom, Coagulation Defect, UBC9, activation by organism of non-apoptotic programmed cell death in other organism, hemolysin activity, Ubc9, Snakebite Envenoming, Proteins, Alpha-dystrobrevin-associated MAGE Protein, disorders, total expressed protein, medical condition, Protein Digestion, Cistrons, Digestions, Peptide, Frozen Plasmas, FBgn0010602, Snake Envenomation, Proteolyses, Mus, endoprotease activity, chemical analysis, Protein, dUbc9, dUBC9, Peptidases, condition, ubc9, Hemolytic Complement, blood coagulation disease, Plasma, Creatin, coagulopathy, RGD1560259, coagulation defect, N-methyl-N-guanylglycine, portion of plasma, House Mice, Blood Coagulation, 219, Laboratory Mice, HF2 -Proteinase, Protein Gene Products, Gene Proteins, Peptidase, Complement Proteins, postpartum coagulation defect with delivery, Snake, blood coagulation, N-(aminoiminomethyl)-N-methyl-, Dmubc9, envenomation perturbing biological process, Peptid, proteinase, assay, response, biopsy, Bothrops jararaca Venoms, Jararaca, Laboratory Mouse, CG3018, DmUbc9PXD039562falseSystemic toxicity of snake venom metalloproteinases: proteomics analyses of kidney injury and blood plasma disturbances in a mouse modelMetalloproteinases are abundant in viperid venoms and are implicated in several envenomation effects. Bothrops jararaca venom is reported to induce kidney injury and coagulopathy. HF3 is an extremely hemorrhagic metalloproteinase from B. jararaca venom and participates in the local pathogenesis of envenomation. Here we applied proteomics approaches to evaluate the effects of HF3 in the mouse kidney and blood plasma after 2 h and 6 h of HF3 injection in the thigh muscle. All proteomic analyses were performed using orbitrap-based high-resolution mass spectrometry. For kidney tissue and plasma proteomic analysis, proteins were extracted and submitted to trypsin digestion and peptides were TMT-labeled for relative quantification. For N-terminomic analysis of kidney tissue, a modified Terminal Amine Isotopic Labeling of Substrates (TAILS) protocol was applied, using TMT-tags for free-amine blocking and relative quantification.Fri Jan 20 01:18:00 GMT 2023MSV00009110137806411