Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease.
Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle...
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ftdoajarticles:oai:doaj.org/article:ea8b152f26a74cc3b0b646fecaac43ec 2023-05-15T15:12:32+02:00 Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. Harry F Williams Ben A Mellows Robert Mitchell Peggy Sfyri Harry J Layfield Maryam Salamah Rajendran Vaiyapuri Henry Collins-Hooper Andrew B Bicknell Antonios Matsakas Ketan Patel Sakthivel Vaiyapuri 2019-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0007041 https://doaj.org/article/ea8b152f26a74cc3b0b646fecaac43ec EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC6368331?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007041 https://doaj.org/article/ea8b152f26a74cc3b0b646fecaac43ec PLoS Neglected Tropical Diseases, Vol 13, Iss 1, p e0007041 (2019) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2019 ftdoajarticles https://doi.org/10.1371/journal.pntd.0007041 2022-12-31T10:18:20Z Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 13 1 e0007041 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Harry F Williams Ben A Mellows Robert Mitchell Peggy Sfyri Harry J Layfield Maryam Salamah Rajendran Vaiyapuri Henry Collins-Hooper Andrew B Bicknell Antonios Matsakas Ketan Patel Sakthivel Vaiyapuri Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Snakebite is a major neglected tropical health issue that affects over 5 million people worldwide resulting in around 1.8 million envenomations and 100,000 deaths each year. Snakebite envenomation also causes innumerable morbidities, specifically loss of limbs as a result of excessive tissue/muscle damage. Snake venom metalloproteases (SVMPs) are a predominant component of viper venoms, and are involved in the degradation of basement membrane proteins (particularly collagen) surrounding the tissues around the bite site. Although their collagenolytic properties have been established, the molecular mechanisms through which SVMPs induce permanent muscle damage are poorly understood. Here, we demonstrate the purification and characterisation of an SVMP from a viper (Crotalus atrox) venom. Mass spectrometry analysis confirmed that this protein is most likely to be a group III metalloprotease (showing high similarity to VAP2A) and has been referred to as CAMP (Crotalus atrox metalloprotease). CAMP displays both collagenolytic and fibrinogenolytic activities and inhibits CRP-XL-induced platelet aggregation. To determine its effects on muscle damage, CAMP was administered into the tibialis anterior muscle of mice and its actions were compared with cardiotoxin I (a three-finger toxin) from an elapid snake (Naja pallida) venom. Extensive immunohistochemistry analyses revealed that CAMP significantly damages skeletal muscles by attacking the collagen scaffold and other important basement membrane proteins, and prevents their regeneration through disrupting the functions of satellite cells. In contrast, cardiotoxin I destroys skeletal muscle by damaging the plasma membrane, but does not impact regeneration due to its inability to affect the extracellular matrix. Overall, this study provides novel insights into the mechanisms through which SVMPs induce permanent muscle damage. |
format |
Article in Journal/Newspaper |
author |
Harry F Williams Ben A Mellows Robert Mitchell Peggy Sfyri Harry J Layfield Maryam Salamah Rajendran Vaiyapuri Henry Collins-Hooper Andrew B Bicknell Antonios Matsakas Ketan Patel Sakthivel Vaiyapuri |
author_facet |
Harry F Williams Ben A Mellows Robert Mitchell Peggy Sfyri Harry J Layfield Maryam Salamah Rajendran Vaiyapuri Henry Collins-Hooper Andrew B Bicknell Antonios Matsakas Ketan Patel Sakthivel Vaiyapuri |
author_sort |
Harry F Williams |
title |
Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. |
title_short |
Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. |
title_full |
Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. |
title_fullStr |
Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. |
title_full_unstemmed |
Mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. |
title_sort |
mechanisms underpinning the permanent muscle damage induced by snake venom metalloprotease. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2019 |
url |
https://doi.org/10.1371/journal.pntd.0007041 https://doaj.org/article/ea8b152f26a74cc3b0b646fecaac43ec |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 13, Iss 1, p e0007041 (2019) |
op_relation |
http://europepmc.org/articles/PMC6368331?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0007041 https://doaj.org/article/ea8b152f26a74cc3b0b646fecaac43ec |
op_doi |
https://doi.org/10.1371/journal.pntd.0007041 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
13 |
container_issue |
1 |
container_start_page |
e0007041 |
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1766343208807170048 |