Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins

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 <i>Bothrops jararaca</i> venom. Studies using proteomic approaches revealed targ...

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Autores principales:	Luciana Bertholim, Alison F. A. Chaves, Ana K. Oliveira, Milene C. Menezes, Amanda F. Asega, Alexandre K. Tashima, Andre Zelanis, Solange M. T. Serrano
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Bothrops jararaca</i> HF3 human plasma proteolysis snake venom metalloproteinase Medicine R
Acceso en línea:	https://doaj.org/article/32f8cf74497f4036b23d6d4e2bae528f
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spelling	oai:doaj.org-article:32f8cf74497f4036b23d6d4e2bae528f2021-11-25T19:08:39ZSystemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins10.3390/toxins131107642072-6651https://doaj.org/article/32f8cf74497f4036b23d6d4e2bae528f2021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/764https://doaj.org/toc/2072-6651Hemorrhage 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 <i>Bothrops jararaca</i> 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.Luciana BertholimAlison F. A. ChavesAna K. OliveiraMilene C. MenezesAmanda F. AsegaAlexandre K. TashimaAndre ZelanisSolange M. T. SerranoMDPI AGarticle<i>Bothrops jararaca</i>HF3human plasmaproteolysissnake venom metalloproteinaseMedicineRENToxins, Vol 13, Iss 764, p 764 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Bothrops jararaca</i> HF3 human plasma proteolysis snake venom metalloproteinase Medicine R
spellingShingle	<i>Bothrops jararaca</i> HF3 human plasma proteolysis snake venom metalloproteinase Medicine R Luciana Bertholim Alison F. A. Chaves Ana K. Oliveira Milene C. Menezes Amanda F. Asega Alexandre K. Tashima Andre Zelanis Solange M. T. Serrano Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins
description	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 <i>Bothrops jararaca</i> 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.
format	article
author	Luciana Bertholim Alison F. A. Chaves Ana K. Oliveira Milene C. Menezes Amanda F. Asega Alexandre K. Tashima Andre Zelanis Solange M. T. Serrano
author_facet	Luciana Bertholim Alison F. A. Chaves Ana K. Oliveira Milene C. Menezes Amanda F. Asega Alexandre K. Tashima Andre Zelanis Solange M. T. Serrano
author_sort	Luciana Bertholim
title	Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins
title_short	Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins
title_full	Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins
title_fullStr	Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins
title_full_unstemmed	Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins
title_sort	systemic effects of hemorrhagic snake venom metalloproteinases: untargeted peptidomics to explore the pathodegradome of plasma proteins
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/32f8cf74497f4036b23d6d4e2bae528f
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Systemic Effects of Hemorrhagic Snake Venom Metalloproteinases: Untargeted Peptidomics to Explore the Pathodegradome of Plasma Proteins

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