P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis
Abstract Background: Snake venoms are composed of pharmacologically active proteins that are evolutionarily diverse, stable and specific to targets. Hence, venoms have been explored as a source of bioactive molecules in treating numerous diseases. Recent evidences suggest that snake venom proteins m...
Published in: | Journal of Venomous Animals and Toxins including Tropical Diseases |
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ftdoajarticles:oai:doaj.org/article:ba329ed15d404646b6c07da318d4ea98 2023-05-15T15:14:37+02:00 P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis Shreesha K. Bhat Manjunath B. Joshi Sampara Vasishta Rajesh N. Jagadale Setlur G. Biligiri Monika A. Coronado Raghuvir K. Arni Kapaettu Satyamoorthy 2021-08-01T00:00:00Z https://doi.org/10.1590/1678-9199-jvatitd-2020-0180 https://doaj.org/article/ba329ed15d404646b6c07da318d4ea98 EN eng SciELO http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100318&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-2020-0180 https://doaj.org/article/ba329ed15d404646b6c07da318d4ea98 Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 27 (2021) P-I metalloproteinases LAAO Bothrops Anti-angiogenic Snake venom Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 article 2021 ftdoajarticles https://doi.org/10.1590/1678-9199-jvatitd-2020-0180 2022-12-31T14:50:30Z Abstract Background: Snake venoms are composed of pharmacologically active proteins that are evolutionarily diverse, stable and specific to targets. Hence, venoms have been explored as a source of bioactive molecules in treating numerous diseases. Recent evidences suggest that snake venom proteins may affect the formation of new blood vessels. Excessive angiogenesis has been implicated in several pathologies including tumours, diabetic retinopathy, arthritis, inter alia. In the present study, we have examined the effects of P-I metalloproteinases isolated from Bothrops moojeni (BmMP-1) and Bothrops atrox (BaMP-1) and L-amino acid oxidases (LAAO) isolated from B. moojeni (BmLAAO) and B. atrox (BaLAAO) on biochemical and functional aspects of angiogenesis. Methods: P-I metalloproteinases and LAAO were purified from venom by molecular size exclusion and ion-exchange chromatography and subsequently confirmed using mass spectrometry. The P-I metalloproteinases were characterized by azocaseinolytic, fibrinogenolytic and gelatinase activity and LAAO activity was assessed by enzyme activity on L-amino acids. Influence of these proteins on apoptosis and cell cycle in endothelial cells was analysed by flow cytometry. The angiogenic activity was determined by in vitro 3D spheroid assay, Matrigel tube forming assay, and in vivo agarose plug transformation in mice. Results: P-I metalloproteinases exhibited azocaseinolytic activity, cleaved α and partially β chain of fibrinogen, and displayed catalytic activity on gelatin. LAAO showed differential activity on L-amino acids. Flow cytometry analysis indicated that both P-I metalloproteinases and LAAO arrested the cells in G0/G1 phase and further induced both necrosis and apoptosis in endothelial cells. In vitro, P-I metalloproteinases and LAAO exhibited significant anti-angiogenic properties in 3D spheroid and Matrigel models by reducing sprout outgrowth and tube formation. Using agarose plug transplants in mice harbouring P-I metalloproteinases and LAAO we demonstrated a ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Journal of Venomous Animals and Toxins including Tropical Diseases 27 |
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Directory of Open Access Journals: DOAJ Articles |
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English |
topic |
P-I metalloproteinases LAAO Bothrops Anti-angiogenic Snake venom Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
spellingShingle |
P-I metalloproteinases LAAO Bothrops Anti-angiogenic Snake venom Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 Shreesha K. Bhat Manjunath B. Joshi Sampara Vasishta Rajesh N. Jagadale Setlur G. Biligiri Monika A. Coronado Raghuvir K. Arni Kapaettu Satyamoorthy P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis |
topic_facet |
P-I metalloproteinases LAAO Bothrops Anti-angiogenic Snake venom Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
description |
Abstract Background: Snake venoms are composed of pharmacologically active proteins that are evolutionarily diverse, stable and specific to targets. Hence, venoms have been explored as a source of bioactive molecules in treating numerous diseases. Recent evidences suggest that snake venom proteins may affect the formation of new blood vessels. Excessive angiogenesis has been implicated in several pathologies including tumours, diabetic retinopathy, arthritis, inter alia. In the present study, we have examined the effects of P-I metalloproteinases isolated from Bothrops moojeni (BmMP-1) and Bothrops atrox (BaMP-1) and L-amino acid oxidases (LAAO) isolated from B. moojeni (BmLAAO) and B. atrox (BaLAAO) on biochemical and functional aspects of angiogenesis. Methods: P-I metalloproteinases and LAAO were purified from venom by molecular size exclusion and ion-exchange chromatography and subsequently confirmed using mass spectrometry. The P-I metalloproteinases were characterized by azocaseinolytic, fibrinogenolytic and gelatinase activity and LAAO activity was assessed by enzyme activity on L-amino acids. Influence of these proteins on apoptosis and cell cycle in endothelial cells was analysed by flow cytometry. The angiogenic activity was determined by in vitro 3D spheroid assay, Matrigel tube forming assay, and in vivo agarose plug transformation in mice. Results: P-I metalloproteinases exhibited azocaseinolytic activity, cleaved α and partially β chain of fibrinogen, and displayed catalytic activity on gelatin. LAAO showed differential activity on L-amino acids. Flow cytometry analysis indicated that both P-I metalloproteinases and LAAO arrested the cells in G0/G1 phase and further induced both necrosis and apoptosis in endothelial cells. In vitro, P-I metalloproteinases and LAAO exhibited significant anti-angiogenic properties in 3D spheroid and Matrigel models by reducing sprout outgrowth and tube formation. Using agarose plug transplants in mice harbouring P-I metalloproteinases and LAAO we demonstrated a ... |
format |
Article in Journal/Newspaper |
author |
Shreesha K. Bhat Manjunath B. Joshi Sampara Vasishta Rajesh N. Jagadale Setlur G. Biligiri Monika A. Coronado Raghuvir K. Arni Kapaettu Satyamoorthy |
author_facet |
Shreesha K. Bhat Manjunath B. Joshi Sampara Vasishta Rajesh N. Jagadale Setlur G. Biligiri Monika A. Coronado Raghuvir K. Arni Kapaettu Satyamoorthy |
author_sort |
Shreesha K. Bhat |
title |
P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis |
title_short |
P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis |
title_full |
P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis |
title_fullStr |
P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis |
title_full_unstemmed |
P-I metalloproteinases and L-amino acid oxidases from Bothrops species inhibit angiogenesis |
title_sort |
p-i metalloproteinases and l-amino acid oxidases from bothrops species inhibit angiogenesis |
publisher |
SciELO |
publishDate |
2021 |
url |
https://doi.org/10.1590/1678-9199-jvatitd-2020-0180 https://doaj.org/article/ba329ed15d404646b6c07da318d4ea98 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 27 (2021) |
op_relation |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100318&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-2020-0180 https://doaj.org/article/ba329ed15d404646b6c07da318d4ea98 |
op_doi |
https://doi.org/10.1590/1678-9199-jvatitd-2020-0180 |
container_title |
Journal of Venomous Animals and Toxins including Tropical Diseases |
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27 |
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1766345048727748608 |