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Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates

SIMPLE SUMMARY: Snakebite envenoming is an important public health issue with annual mortality rates ranging between 81,000 and 138,000. Snake venoms may cause a range of pathophysiological effects and may have tissue-damaging activities that result in lifelong morbidities. The tissue-damaging compo...

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Autores principales: Bittenbinder, Mátyás A., Bergkamp, Nick D., Slagboom, Julien, Bebelman, Jan Paul M., Casewell, Nicholas R., Siderius, Marco H., Smit, Martine J., Kool, Jeroen, Vonk, Freek J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295075/
https://www.ncbi.nlm.nih.gov/pubmed/37372050
http://dx.doi.org/10.3390/biology12060765
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author Bittenbinder, Mátyás A.
Bergkamp, Nick D.
Slagboom, Julien
Bebelman, Jan Paul M.
Casewell, Nicholas R.
Siderius, Marco H.
Smit, Martine J.
Kool, Jeroen
Vonk, Freek J.
author_facet Bittenbinder, Mátyás A.
Bergkamp, Nick D.
Slagboom, Julien
Bebelman, Jan Paul M.
Casewell, Nicholas R.
Siderius, Marco H.
Smit, Martine J.
Kool, Jeroen
Vonk, Freek J.
author_sort Bittenbinder, Mátyás A.
collection PubMed
description SIMPLE SUMMARY: Snakebite envenoming is an important public health issue with annual mortality rates ranging between 81,000 and 138,000. Snake venoms may cause a range of pathophysiological effects and may have tissue-damaging activities that result in lifelong morbidities. The tissue-damaging components in snake venoms comprise multiple toxin classes with various molecular targets including cellular membranes and the extracellular matrix (ECM). In this study, we present multiple assay formats that enable us to study ECM degradation using a variety of fluorescently labeled ECM components. This workflow could provide valuable insights into the key mechanisms by which proteolytic venom components exert their effects. The workflow could prove useful for the development of effective snakebite treatments. ABSTRACT: Snakebite envenoming is an important public health issue with devastating consequences and annual mortality rates that range between 81,000 and 138,000. Snake venoms may cause a range of pathophysiological effects affecting the nervous system and the cardiovascular system. Moreover, snake venom may have tissue-damaging activities that result in lifelong morbidities such as amputations, muscle degeneration, and organ malfunctioning. The tissue-damaging components in snake venoms comprise multiple toxin classes with various molecular targets including cellular membranes and the extracellular matrix (ECM). In this study, we present multiple assay formats that enable investigation of snake venom-induced ECM degradation using a variety of (dye-quenched) fluorescently labeled ECM components. Using a combinatorial approach, we were able to characterise different proteolytic profiles for different medically relevant snake venoms, followed by identification of the responsible components within the snake venoms. This workflow could provide valuable insights into the key mechanisms by which proteolytic venom components exert their effects and could therefore prove useful for the development of effective snakebite treatments against this severe pathology.
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spelling pubmed-102950752023-06-28 Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates Bittenbinder, Mátyás A. Bergkamp, Nick D. Slagboom, Julien Bebelman, Jan Paul M. Casewell, Nicholas R. Siderius, Marco H. Smit, Martine J. Kool, Jeroen Vonk, Freek J. Biology (Basel) Article SIMPLE SUMMARY: Snakebite envenoming is an important public health issue with annual mortality rates ranging between 81,000 and 138,000. Snake venoms may cause a range of pathophysiological effects and may have tissue-damaging activities that result in lifelong morbidities. The tissue-damaging components in snake venoms comprise multiple toxin classes with various molecular targets including cellular membranes and the extracellular matrix (ECM). In this study, we present multiple assay formats that enable us to study ECM degradation using a variety of fluorescently labeled ECM components. This workflow could provide valuable insights into the key mechanisms by which proteolytic venom components exert their effects. The workflow could prove useful for the development of effective snakebite treatments. ABSTRACT: Snakebite envenoming is an important public health issue with devastating consequences and annual mortality rates that range between 81,000 and 138,000. Snake venoms may cause a range of pathophysiological effects affecting the nervous system and the cardiovascular system. Moreover, snake venom may have tissue-damaging activities that result in lifelong morbidities such as amputations, muscle degeneration, and organ malfunctioning. The tissue-damaging components in snake venoms comprise multiple toxin classes with various molecular targets including cellular membranes and the extracellular matrix (ECM). In this study, we present multiple assay formats that enable investigation of snake venom-induced ECM degradation using a variety of (dye-quenched) fluorescently labeled ECM components. Using a combinatorial approach, we were able to characterise different proteolytic profiles for different medically relevant snake venoms, followed by identification of the responsible components within the snake venoms. This workflow could provide valuable insights into the key mechanisms by which proteolytic venom components exert their effects and could therefore prove useful for the development of effective snakebite treatments against this severe pathology. MDPI 2023-05-24 /pmc/articles/PMC10295075/ /pubmed/37372050 http://dx.doi.org/10.3390/biology12060765 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bittenbinder, Mátyás A.
Bergkamp, Nick D.
Slagboom, Julien
Bebelman, Jan Paul M.
Casewell, Nicholas R.
Siderius, Marco H.
Smit, Martine J.
Kool, Jeroen
Vonk, Freek J.
Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates
title Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates
title_full Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates
title_fullStr Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates
title_full_unstemmed Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates
title_short Monitoring Snake Venom-Induced Extracellular Matrix Degradation and Identifying Proteolytically Active Venom Toxins Using Fluorescently Labeled Substrates
title_sort monitoring snake venom-induced extracellular matrix degradation and identifying proteolytically active venom toxins using fluorescently labeled substrates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10295075/
https://www.ncbi.nlm.nih.gov/pubmed/37372050
http://dx.doi.org/10.3390/biology12060765
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