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Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins
Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhan...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221120/ https://www.ncbi.nlm.nih.gov/pubmed/32457615 http://dx.doi.org/10.3389/fphar.2020.00611 |
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author | Pucca, Manuela B. Ahmadi, Shirin Cerni, Felipe A. Ledsgaard, Line Sørensen, Christoffer V. McGeoghan, Farrell T. S. Stewart, Trenton Schoof, Erwin Lomonte, Bruno auf dem Keller, Ulrich Arantes, Eliane C. Çalışkan, Figen Laustsen, Andreas H. |
author_facet | Pucca, Manuela B. Ahmadi, Shirin Cerni, Felipe A. Ledsgaard, Line Sørensen, Christoffer V. McGeoghan, Farrell T. S. Stewart, Trenton Schoof, Erwin Lomonte, Bruno auf dem Keller, Ulrich Arantes, Eliane C. Çalışkan, Figen Laustsen, Andreas H. |
author_sort | Pucca, Manuela B. |
collection | PubMed |
description | Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhanced toxicity with a metabolic advantage, since less venom is needed to inflict potent toxic effects in prey and predators. Among the toxins that are known for interacting synergistically are cytotoxins from snake venoms, phospholipases A(2) from snake and bee venoms, and melittin from bee venom. These toxins may derive a synergistically enhanced toxicity via formation of toxin complexes by hetero-oligomerization. Using a human keratinocyte assay mimicking human epidermis in vitro, we demonstrate and quantify the level of synergistically enhanced toxicity for 12 cytotoxin/melittin-PLA(2) combinations using toxins from elapids, vipers, and bees. Moreover, by utilizing an interaction-based assay and by including a wealth of information obtained via a thorough literature review, we speculate and propose a mechanistic model for how toxin synergism in relation to cytotoxicity may be mediated by cytotoxin/melittin and PLA(2) complex formation. |
format | Online Article Text |
id | pubmed-7221120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72211202020-05-25 Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins Pucca, Manuela B. Ahmadi, Shirin Cerni, Felipe A. Ledsgaard, Line Sørensen, Christoffer V. McGeoghan, Farrell T. S. Stewart, Trenton Schoof, Erwin Lomonte, Bruno auf dem Keller, Ulrich Arantes, Eliane C. Çalışkan, Figen Laustsen, Andreas H. Front Pharmacol Pharmacology Toxin synergism is a complex biochemical phenomenon, where different animal venom proteins interact either directly or indirectly to potentiate toxicity to a level that is above the sum of the toxicities of the individual toxins. This provides the animals possessing venoms with synergistically enhanced toxicity with a metabolic advantage, since less venom is needed to inflict potent toxic effects in prey and predators. Among the toxins that are known for interacting synergistically are cytotoxins from snake venoms, phospholipases A(2) from snake and bee venoms, and melittin from bee venom. These toxins may derive a synergistically enhanced toxicity via formation of toxin complexes by hetero-oligomerization. Using a human keratinocyte assay mimicking human epidermis in vitro, we demonstrate and quantify the level of synergistically enhanced toxicity for 12 cytotoxin/melittin-PLA(2) combinations using toxins from elapids, vipers, and bees. Moreover, by utilizing an interaction-based assay and by including a wealth of information obtained via a thorough literature review, we speculate and propose a mechanistic model for how toxin synergism in relation to cytotoxicity may be mediated by cytotoxin/melittin and PLA(2) complex formation. Frontiers Media S.A. 2020-05-07 /pmc/articles/PMC7221120/ /pubmed/32457615 http://dx.doi.org/10.3389/fphar.2020.00611 Text en Copyright © 2020 Pucca, Ahmadi, Cerni, Ledsgaard, Sørensen, McGeoghan, Stewart, Schoof, Lomonte, auf dem Keller, Arantes, Çalışkan and Laustsen http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Pucca, Manuela B. Ahmadi, Shirin Cerni, Felipe A. Ledsgaard, Line Sørensen, Christoffer V. McGeoghan, Farrell T. S. Stewart, Trenton Schoof, Erwin Lomonte, Bruno auf dem Keller, Ulrich Arantes, Eliane C. Çalışkan, Figen Laustsen, Andreas H. Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins |
title | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins |
title_full | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins |
title_fullStr | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins |
title_full_unstemmed | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins |
title_short | Unity Makes Strength: Exploring Intraspecies and Interspecies Toxin Synergism between Phospholipases A(2) and Cytotoxins |
title_sort | unity makes strength: exploring intraspecies and interspecies toxin synergism between phospholipases a(2) and cytotoxins |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7221120/ https://www.ncbi.nlm.nih.gov/pubmed/32457615 http://dx.doi.org/10.3389/fphar.2020.00611 |
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