{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T13:44:38Z","timestamp":1777383878663,"version":"3.51.4"},"reference-count":110,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2011\/16623-1; 2011\/08514-8; 2013\/07467-1; 2020\/12317-2"],"award-info":[{"award-number":["2011\/16623-1; 2011\/08514-8; 2013\/07467-1; 2020\/12317-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico (CNPq)","award":["308133\/2015-3"],"award-info":[{"award-number":["308133\/2015-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Hemorrhage induced by snake venom metalloproteinases (SVMPs) is a complex phenomenon that involves capillary disruption and blood extravasation. HF3 (hemorrhagic factor 3) is an extremely hemorrhagic SVMP of Bothrops jararaca venom. Studies using proteomic approaches revealed targets of HF3 among intracellular and extracellular proteins. However, the role of the cleavage of plasma proteins in the context of the hemorrhage remains not fully understood. The main goal of this study was to analyze the degradome of HF3 in human plasma. For this purpose, approaches for the depletion of the most abundant proteins, and for the enrichment of low abundant proteins of human plasma, were used to minimize the dynamic range of protein concentration, in order to assess the proteolytic activity of HF3 on a wide spectrum of proteins, and to detect the degradation products using mass spectrometry-based untargeted peptidomics. The results revealed the hydrolysis products generated by HF3 and allowed the identification of cleavage sites. A total of 61 plasma proteins were identified as cleaved by HF3. Some of these proteins corroborate previous studies, and others are new HF3 targets, including proteins of the coagulation cascade, of the complement system, proteins acting on the modulation of inflammation, and plasma proteinase inhibitors. Overall, the data indicate that HF3 escapes inhibition and sculpts the plasma proteome by degrading key proteins and generating peptides that may act synergistically in the hemorrhagic process.<\/jats:p>","DOI":"10.3390\/toxins13110764","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T23:52:35Z","timestamp":1635465155000},"page":"764","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins"],"prefix":"10.3390","volume":"13","author":[{"given":"Luciana","family":"Bertholim","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalig, CeTICS, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison F. A.","family":"Chaves","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalig, CeTICS, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6837-5739","authenticated-orcid":false,"given":"Ana K.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalig, CeTICS, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1923-9113","authenticated-orcid":false,"given":"Milene C.","family":"Menezes","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalig, CeTICS, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amanda F.","family":"Asega","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalig, CeTICS, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre K.","family":"Tashima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Escola Paulista de Medicina, Federal University of Sao Paulo, Sao Paulo 04023-901, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andre","family":"Zelanis","sequence":"additional","affiliation":[{"name":"Functional Proteomics Laboratory, Department of Science and Technology, Federal University of S\u00e3o Paulo (UNIFESP), 330 Talim St., S\u00e3o Jos\u00e9 dos Campos 12231-280, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8994-1904","authenticated-orcid":false,"given":"Solange M. T.","family":"Serrano","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Toxinologia Aplicada, Center of Toxins, Immune-Response and Cell Signalig, CeTICS, Instituto Butantan, S\u00e3o Paulo 05503-900, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Guti\u00e9rrez, J.M., Escalante, T., Rucavado, A., and Herrera, C. (2016). Hemorrhage caused by snake venom metalloproteinases: A journey of discovery and understanding. Toxins, 8.","DOI":"10.3390\/toxins8040093"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kasturiratne, A., Wickremasinghe, A.R., De Silva, N., Gunawardena, N.K., Pathmeswaran, A., Premaratna, R., Savioli, L., Lalloo, D.G., and De Silva, H.J. (2008). The global burden of snakebite: A literature analysis and modelling based on regional estimates of envenoming and deaths. 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