Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor
PIVL is a Kunitz-type serine protease inhibitor that was previously characterized from Tunisian snake venom, <i>Macrovipera lebetina transmediterranea</i>. It reduced glioblastoma cells’ development and significantly blocked angiogenesis in in-vitro and ex-vivo models. PIVL exerted these...
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MDPI AG
2022-02-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/14/3/170 |
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| author | Maram Morjen Wassim Moslah Imen Touihri-Baraketi Najet Srairi-Abid José Luis Naziha Marrakchi Jed Jebali |
| author_facet | Maram Morjen Wassim Moslah Imen Touihri-Baraketi Najet Srairi-Abid José Luis Naziha Marrakchi Jed Jebali |
| author_sort | Maram Morjen |
| collection | DOAJ |
| description | PIVL is a Kunitz-type serine protease inhibitor that was previously characterized from Tunisian snake venom, <i>Macrovipera lebetina transmediterranea</i>. It reduced glioblastoma cells’ development and significantly blocked angiogenesis in in-vitro and ex-vivo models. PIVL exerted these effects by interfering with αvβ3 integrin. In order to produce a biological active recombinant, the cDNA cloning and expression of PIVL was performed in <i>Escherichia coli</i> (BL21)-DE3 cells using pET-22b (+) vector. The recombinant PIVL protein (rPIVL) was purified by nickel affinity chromatography and has recognized monoclonal anti-His antibody. Functionally, rPIVL exhibited potent anti-tumor cell effects as well as anti-angiogenesis properties. Interestingly, we found that both native PIVL (nPIVL) and rPIVL modulated PI3/AKT and MAPK signaling pathways. In all, our results showed that we have successfully expressed the first active anti-oncogenic snake venom Kunitz-type protease inhibitor that can be a potential therapeutic drug against glioblastoma, in its native or recombinant form. |
| first_indexed | 2024-03-09T12:22:40Z |
| format | Article |
| id | doaj.art-4735568b94a5436bb60f5c1bd5c35461 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-09T12:22:40Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-4735568b94a5436bb60f5c1bd5c354612023-11-30T22:39:00ZengMDPI AGToxins2072-66512022-02-0114317010.3390/toxins14030170Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease InhibitorMaram Morjen0Wassim Moslah1Imen Touihri-Baraketi2Najet Srairi-Abid3José Luis4Naziha Marrakchi5Jed Jebali6Laboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, TunisiaLaboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, TunisiaLaboratoire des Substances Naturelles, Institut National de Recherche et d’Analyse Physico-Chimique (INRAP), Sidi Thabet, Ariana 2020, TunisiaLaboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, TunisiaCNRS-UMR 7051, Institut de Neuro Physiopathologie (INP), Université Aix-Marseille, 27 Bd Jean Moulin, 13385 Marseille, FranceLaboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, TunisiaLaboratory of Biomolecules, Venoms and Theranostic Applications, LR20IPT01, Pasteur Institute of Tunis, University of Tunis El Manar, Tunis 1002, TunisiaPIVL is a Kunitz-type serine protease inhibitor that was previously characterized from Tunisian snake venom, <i>Macrovipera lebetina transmediterranea</i>. It reduced glioblastoma cells’ development and significantly blocked angiogenesis in in-vitro and ex-vivo models. PIVL exerted these effects by interfering with αvβ3 integrin. In order to produce a biological active recombinant, the cDNA cloning and expression of PIVL was performed in <i>Escherichia coli</i> (BL21)-DE3 cells using pET-22b (+) vector. The recombinant PIVL protein (rPIVL) was purified by nickel affinity chromatography and has recognized monoclonal anti-His antibody. Functionally, rPIVL exhibited potent anti-tumor cell effects as well as anti-angiogenesis properties. Interestingly, we found that both native PIVL (nPIVL) and rPIVL modulated PI3/AKT and MAPK signaling pathways. In all, our results showed that we have successfully expressed the first active anti-oncogenic snake venom Kunitz-type protease inhibitor that can be a potential therapeutic drug against glioblastoma, in its native or recombinant form.https://www.mdpi.com/2072-6651/14/3/170snake venomKunitz-type serine protease inhibitorrecombinant PIVLtumorogenesis |
| spellingShingle | Maram Morjen Wassim Moslah Imen Touihri-Baraketi Najet Srairi-Abid José Luis Naziha Marrakchi Jed Jebali Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor Toxins snake venom Kunitz-type serine protease inhibitor recombinant PIVL tumorogenesis |
| title | Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor |
| title_full | Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor |
| title_fullStr | Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor |
| title_full_unstemmed | Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor |
| title_short | Expression of the First Recombinant Anti-Tumoral Snake Venom Kunitz-Type Serine Protease Inhibitor |
| title_sort | expression of the first recombinant anti tumoral snake venom kunitz type serine protease inhibitor |
| topic | snake venom Kunitz-type serine protease inhibitor recombinant PIVL tumorogenesis |
| url | https://www.mdpi.com/2072-6651/14/3/170 |
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