Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus

Abstract Viperid snake venoms contain a unique family of cytotoxic proteins, the Lys49 PLA2 homologs, which are devoid of enzymatic activity but disrupt the integrity of cell membranes. They are known to induce skeletal muscle damage and are therefore named ‘myotoxins’. Single intact and skinned (de...

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Autores principales:	Alfredo Jesús López-Dávila, Natalie Weber, Theresia Kraft, Faramarz Matinmehr, Mariela Arias-Hidalgo, Julián Fernández, Bruno Lomonte, José María Gutiérrez
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cc35569f21c0463fa051d26b773f6b04
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spelling	oai:doaj.org-article:cc35569f21c0463fa051d26b773f6b042021-12-02T17:17:39ZCytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus10.1038/s41598-021-98594-52045-2322https://doaj.org/article/cc35569f21c0463fa051d26b773f6b042021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98594-5https://doaj.org/toc/2045-2322Abstract Viperid snake venoms contain a unique family of cytotoxic proteins, the Lys49 PLA2 homologs, which are devoid of enzymatic activity but disrupt the integrity of cell membranes. They are known to induce skeletal muscle damage and are therefore named ‘myotoxins’. Single intact and skinned (devoid of membranes and cytoplasm but with intact sarcomeric proteins) rat cardiomyocytes were used to analyze the cytotoxic action of a myotoxin, from the venom of Bothrops asper. The toxin induced rapid hypercontraction of intact cardiomyocytes, associated with an increase in the cytosolic concentration of calcium and with cell membrane disruption. Hypercontraction of intact cardiomyocytes was abrogated by the myosin inhibitor para-aminoblebbistatin (AmBleb). No toxin-induced changes of key parameters of force development were observed in skinned cardiomyocytes. Thus, although myosin is a key effector of the observed hypercontraction, a direct effect of the toxin on the sarcomeric proteins -including the actomyosin complex- is not part of the mechanism of cytotoxicity. Owing to the sensitivity of intact cardiomyocytes to the cytotoxic action of myotoxin, this ex vivo model is a valuable tool to explore in further detail the mechanism of action of this group of snake venom toxins.Alfredo Jesús López-DávilaNatalie WeberTheresia KraftFaramarz MatinmehrMariela Arias-HidalgoJulián FernándezBruno LomonteJosé María GutiérrezNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alfredo Jesús López-Dávila Natalie Weber Theresia Kraft Faramarz Matinmehr Mariela Arias-Hidalgo Julián Fernández Bruno Lomonte José María Gutiérrez Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
description	Abstract Viperid snake venoms contain a unique family of cytotoxic proteins, the Lys49 PLA2 homologs, which are devoid of enzymatic activity but disrupt the integrity of cell membranes. They are known to induce skeletal muscle damage and are therefore named ‘myotoxins’. Single intact and skinned (devoid of membranes and cytoplasm but with intact sarcomeric proteins) rat cardiomyocytes were used to analyze the cytotoxic action of a myotoxin, from the venom of Bothrops asper. The toxin induced rapid hypercontraction of intact cardiomyocytes, associated with an increase in the cytosolic concentration of calcium and with cell membrane disruption. Hypercontraction of intact cardiomyocytes was abrogated by the myosin inhibitor para-aminoblebbistatin (AmBleb). No toxin-induced changes of key parameters of force development were observed in skinned cardiomyocytes. Thus, although myosin is a key effector of the observed hypercontraction, a direct effect of the toxin on the sarcomeric proteins -including the actomyosin complex- is not part of the mechanism of cytotoxicity. Owing to the sensitivity of intact cardiomyocytes to the cytotoxic action of myotoxin, this ex vivo model is a valuable tool to explore in further detail the mechanism of action of this group of snake venom toxins.
format	article
author	Alfredo Jesús López-Dávila Natalie Weber Theresia Kraft Faramarz Matinmehr Mariela Arias-Hidalgo Julián Fernández Bruno Lomonte José María Gutiérrez
author_facet	Alfredo Jesús López-Dávila Natalie Weber Theresia Kraft Faramarz Matinmehr Mariela Arias-Hidalgo Julián Fernández Bruno Lomonte José María Gutiérrez
author_sort	Alfredo Jesús López-Dávila
title	Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
title_short	Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
title_full	Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
title_fullStr	Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
title_full_unstemmed	Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
title_sort	cytotoxicity of snake venom lys49 pla2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cc35569f21c0463fa051d26b773f6b04
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Cytotoxicity of snake venom Lys49 PLA2-like myotoxin on rat cardiomyocytes ex vivo does not involve a direct action on the contractile apparatus

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