CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo.
Identifieur interne : 000097 ( Main/Exploration ); précédent : 000096; suivant : 000098CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo.
Auteurs : Raoudha Kessentini-Zouari [Tunisie] ; Jed Jebali ; Salma Taboubi ; Najet Srairi-Abid ; Maram Morjen ; Olfa Kallech-Ziri ; Sofiane Bezzine ; Jacques Marvaldi ; Mohamed El Ayeb ; Naziha Marrakchi ; José LuisSource :
- Laboratory investigation; a journal of technical methods and pathology [ 1530-0307 ] ; 2010.
Descripteurs français
- KwdFr :
- Animaux (MeSH), Cellules endothéliales (MeSH), Chorioallantoïde (effets des médicaments et des substances chimiques), Contacts focaux (effets des médicaments et des substances chimiques), Group I Phospholipases A2 (composition chimique), Group I Phospholipases A2 (pharmacologie), Group II Phospholipases A2 (composition chimique), Group II Phospholipases A2 (pharmacologie), Humains (MeSH), Inhibiteurs de l'angiogenèse (pharmacologie), Intégrines (effets des médicaments et des substances chimiques), Maquettes de structure (MeSH), Techniques in vitro (MeSH), Venins de vipère (composition chimique), Venins de vipère (enzymologie), Électricité statique (MeSH).
- MESH :
- composition chimique : Group I Phospholipases A2, Group II Phospholipases A2, Venins de vipère.
- effets des médicaments et des substances chimiques : Chorioallantoïde, Contacts focaux, Intégrines.
- enzymologie : Venins de vipère.
- pharmacologie : Group I Phospholipases A2, Group II Phospholipases A2, Inhibiteurs de l'angiogenèse.
- Animaux, Cellules endothéliales, Humains, Maquettes de structure, Techniques in vitro, Électricité statique.
English descriptors
- KwdEn :
- Angiogenesis Inhibitors (pharmacology), Animals (MeSH), Chorioallantoic Membrane (drug effects), Endothelial Cells (MeSH), Focal Adhesions (drug effects), Group I Phospholipases A2 (chemistry), Group I Phospholipases A2 (pharmacology), Group II Phospholipases A2 (chemistry), Group II Phospholipases A2 (pharmacology), Humans (MeSH), In Vitro Techniques (MeSH), Integrins (drug effects), Models, Structural (MeSH), Static Electricity (MeSH), Viper Venoms (chemistry), Viper Venoms (enzymology).
- MESH :
- chemical , chemistry : Group I Phospholipases A2, Group II Phospholipases A2, Viper Venoms.
- chemical , drug effects : Integrins.
- chemical , enzymology : Viper Venoms.
- chemical , pharmacology : Angiogenesis Inhibitors, Group I Phospholipases A2, Group II Phospholipases A2.
- drug effects : Chorioallantoic Membrane, Focal Adhesions.
- Animals, Endothelial Cells, Humans, In Vitro Techniques, Models, Structural, Static Electricity.
Abstract
Integrins are essential in the complex multistep process of angiogenesis and are thus attractive targets for the development of antiangiogenic therapies. Integrins are antagonized by disintegrins and C-type lectin-like proteins, two protein families from snake venom. Here, we report that CC-PLA2-1 and CC-PLA2-2, two novel secreted phospholipases A(2) (PLA(2)) isolated from Cerastes cerastes venom, also showed anti-integrin activity. Indeed, both PLA(2)s efficiently inhibited human brain microvascular endothelial cell adhesion and migration to fibrinogen and fibronectin in a dose-dependent manner. Interestingly, we show that this anti-adhesive effect was mediated by alpha5beta1 and alphav-containing integrins. CC-PLA2s also impaired in vitro human brain microvascular endothelial cell tubulogenesis on Matrigel and showed antiangiogenic activity in vivo in chicken chorioallantoic membrane assay. The complete PLA(2) cDNAs were cloned from a venom gland cDNA library. Mature CC-PLA2-1 and CC-PLA2-2 contain 121 and 120 amino acids, respectively, including 14 cysteines each and showed 83% identity. Tertiary model structures of CC-PLA2-1 and CC-PLA2-2 were generated by homology modeling. This is thus the first study describing an antiangiogenic effect for snake venom PLA(2)s and reporting first clues to their mechanism of action on endothelial cells.
DOI: 10.1038/labinvest.2009.137
PubMed: 20142800
Affiliations:
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uniqKey="Taboubi S" first="Salma" last="Taboubi">Salma Taboubi</name></author><author><name sortKey="Srairi Abid, Najet" sort="Srairi Abid, Najet" uniqKey="Srairi Abid N" first="Najet" last="Srairi-Abid">Najet Srairi-Abid</name></author><author><name sortKey="Morjen, Maram" sort="Morjen, Maram" uniqKey="Morjen M" first="Maram" last="Morjen">Maram Morjen</name></author><author><name sortKey="Kallech Ziri, Olfa" sort="Kallech Ziri, Olfa" uniqKey="Kallech Ziri O" first="Olfa" last="Kallech-Ziri">Olfa Kallech-Ziri</name></author><author><name sortKey="Bezzine, Sofiane" sort="Bezzine, Sofiane" uniqKey="Bezzine S" first="Sofiane" last="Bezzine">Sofiane Bezzine</name></author><author><name sortKey="Marvaldi, Jacques" sort="Marvaldi, Jacques" uniqKey="Marvaldi J" first="Jacques" last="Marvaldi">Jacques Marvaldi</name></author><author><name sortKey="El Ayeb, Mohamed" sort="El Ayeb, Mohamed" uniqKey="El Ayeb M" first="Mohamed" last="El Ayeb">Mohamed El Ayeb</name></author><author><name 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last="Jebali">Jed Jebali</name></author><author><name sortKey="Taboubi, Salma" sort="Taboubi, Salma" uniqKey="Taboubi S" first="Salma" last="Taboubi">Salma Taboubi</name></author><author><name sortKey="Srairi Abid, Najet" sort="Srairi Abid, Najet" uniqKey="Srairi Abid N" first="Najet" last="Srairi-Abid">Najet Srairi-Abid</name></author><author><name sortKey="Morjen, Maram" sort="Morjen, Maram" uniqKey="Morjen M" first="Maram" last="Morjen">Maram Morjen</name></author><author><name sortKey="Kallech Ziri, Olfa" sort="Kallech Ziri, Olfa" uniqKey="Kallech Ziri O" first="Olfa" last="Kallech-Ziri">Olfa Kallech-Ziri</name></author><author><name sortKey="Bezzine, Sofiane" sort="Bezzine, Sofiane" uniqKey="Bezzine S" first="Sofiane" last="Bezzine">Sofiane Bezzine</name></author><author><name sortKey="Marvaldi, Jacques" sort="Marvaldi, Jacques" uniqKey="Marvaldi J" first="Jacques" last="Marvaldi">Jacques Marvaldi</name></author><author><name sortKey="El Ayeb, Mohamed" sort="El Ayeb, Mohamed" uniqKey="El Ayeb M" first="Mohamed" last="El Ayeb">Mohamed El Ayeb</name></author><author><name sortKey="Marrakchi, Naziha" sort="Marrakchi, Naziha" uniqKey="Marrakchi N" first="Naziha" last="Marrakchi">Naziha Marrakchi</name></author><author><name sortKey="Luis, Jose" sort="Luis, Jose" uniqKey="Luis J" first="José" last="Luis">José Luis</name></author></analytic><series><title level="j">Laboratory investigation; a journal of technical methods and pathology</title><idno type="eISSN">1530-0307</idno><imprint><date when="2010" type="published">2010</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Angiogenesis Inhibitors (pharmacology)</term><term>Animals (MeSH)</term><term>Chorioallantoic Membrane (drug effects)</term><term>Endothelial Cells (MeSH)</term><term>Focal Adhesions (drug effects)</term><term>Group I Phospholipases A2 (chemistry)</term><term>Group I Phospholipases A2 (pharmacology)</term><term>Group II Phospholipases A2 (chemistry)</term><term>Group II Phospholipases A2 (pharmacology)</term><term>Humans (MeSH)</term><term>In Vitro Techniques (MeSH)</term><term>Integrins (drug effects)</term><term>Models, Structural (MeSH)</term><term>Static Electricity (MeSH)</term><term>Viper Venoms (chemistry)</term><term>Viper Venoms (enzymology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux (MeSH)</term><term>Cellules endothéliales (MeSH)</term><term>Chorioallantoïde (effets des médicaments et des substances chimiques)</term><term>Contacts focaux (effets des médicaments et des substances chimiques)</term><term>Group I Phospholipases A2 (composition chimique)</term><term>Group I Phospholipases A2 (pharmacologie)</term><term>Group II Phospholipases A2 (composition chimique)</term><term>Group II Phospholipases A2 (pharmacologie)</term><term>Humains (MeSH)</term><term>Inhibiteurs de l'angiogenèse (pharmacologie)</term><term>Intégrines (effets des médicaments et des substances chimiques)</term><term>Maquettes de structure (MeSH)</term><term>Techniques in vitro (MeSH)</term><term>Venins de vipère (composition chimique)</term><term>Venins de vipère (enzymologie)</term><term>Électricité statique (MeSH)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="chemistry" xml:lang="en"><term>Group I Phospholipases A2</term><term>Group II Phospholipases A2</term><term>Viper Venoms</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Integrins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="enzymology" xml:lang="en"><term>Viper Venoms</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Angiogenesis Inhibitors</term><term>Group I Phospholipases A2</term><term>Group II Phospholipases A2</term></keywords><keywords scheme="MESH" qualifier="composition chimique" xml:lang="fr"><term>Group I Phospholipases A2</term><term>Group II Phospholipases A2</term><term>Venins de vipère</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Chorioallantoic Membrane</term><term>Focal Adhesions</term></keywords><keywords scheme="MESH" qualifier="effets des médicaments et des substances chimiques" xml:lang="fr"><term>Chorioallantoïde</term><term>Contacts focaux</term><term>Intégrines</term></keywords><keywords scheme="MESH" qualifier="enzymologie" xml:lang="fr"><term>Venins de vipère</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Group I Phospholipases A2</term><term>Group II Phospholipases A2</term><term>Inhibiteurs de l'angiogenèse</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Endothelial Cells</term><term>Humans</term><term>In Vitro Techniques</term><term>Models, Structural</term><term>Static Electricity</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Cellules endothéliales</term><term>Humains</term><term>Maquettes de structure</term><term>Techniques in vitro</term><term>Électricité statique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Integrins are essential in the complex multistep process of angiogenesis and are thus attractive targets for the development of antiangiogenic therapies. Integrins are antagonized by disintegrins and C-type lectin-like proteins, two protein families from snake venom. Here, we report that CC-PLA2-1 and CC-PLA2-2, two novel secreted phospholipases A(2) (PLA(2)) isolated from Cerastes cerastes venom, also showed anti-integrin activity. Indeed, both PLA(2)s efficiently inhibited human brain microvascular endothelial cell adhesion and migration to fibrinogen and fibronectin in a dose-dependent manner. Interestingly, we show that this anti-adhesive effect was mediated by alpha5beta1 and alphav-containing integrins. CC-PLA2s also impaired in vitro human brain microvascular endothelial cell tubulogenesis on Matrigel and showed antiangiogenic activity in vivo in chicken chorioallantoic membrane assay. The complete PLA(2) cDNAs were cloned from a venom gland cDNA library. Mature CC-PLA2-1 and CC-PLA2-2 contain 121 and 120 amino acids, respectively, including 14 cysteines each and showed 83% identity. Tertiary model structures of CC-PLA2-1 and CC-PLA2-2 were generated by homology modeling. This is thus the first study describing an antiangiogenic effect for snake venom PLA(2)s and reporting first clues to their mechanism of action on endothelial cells.</div></front></TEI><affiliations><list><country><li>Tunisie</li></country><region><li>Gouvernorat de Tunis</li></region><settlement><li>Tunis</li></settlement></list><tree><noCountry><name sortKey="Bezzine, Sofiane" sort="Bezzine, Sofiane" uniqKey="Bezzine S" first="Sofiane" last="Bezzine">Sofiane Bezzine</name><name sortKey="El Ayeb, Mohamed" sort="El Ayeb, Mohamed" uniqKey="El Ayeb M" first="Mohamed" last="El Ayeb">Mohamed El Ayeb</name><name sortKey="Jebali, Jed" sort="Jebali, Jed" uniqKey="Jebali J" first="Jed" last="Jebali">Jed Jebali</name><name sortKey="Kallech Ziri, Olfa" sort="Kallech Ziri, Olfa" uniqKey="Kallech Ziri O" first="Olfa" last="Kallech-Ziri">Olfa Kallech-Ziri</name><name sortKey="Luis, Jose" sort="Luis, Jose" uniqKey="Luis J" first="José" last="Luis">José Luis</name><name sortKey="Marrakchi, Naziha" sort="Marrakchi, Naziha" uniqKey="Marrakchi N" first="Naziha" last="Marrakchi">Naziha Marrakchi</name><name sortKey="Marvaldi, Jacques" sort="Marvaldi, Jacques" uniqKey="Marvaldi J" first="Jacques" last="Marvaldi">Jacques Marvaldi</name><name sortKey="Morjen, Maram" sort="Morjen, Maram" uniqKey="Morjen M" first="Maram" last="Morjen">Maram Morjen</name><name sortKey="Srairi Abid, Najet" sort="Srairi Abid, Najet" uniqKey="Srairi Abid N" first="Najet" last="Srairi-Abid">Najet Srairi-Abid</name><name sortKey="Taboubi, Salma" sort="Taboubi, Salma" uniqKey="Taboubi S" first="Salma" last="Taboubi">Salma Taboubi</name></noCountry><country name="Tunisie"><region name="Gouvernorat de Tunis"><name sortKey="Kessentini Zouari, Raoudha" sort="Kessentini Zouari, Raoudha" uniqKey="Kessentini Zouari R" first="Raoudha" last="Kessentini-Zouari">Raoudha Kessentini-Zouari</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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