CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo.

Raoudha Kessentini-Zouari; Jed Jebali; Salma Taboubi; Najet Srairi-Abid; Maram Morjen; Olfa Kallech-Ziri; Sofiane Bezzine; Jacques Marvaldi; Mohamed El Ayeb; Naziha Marrakchi; José Luis

CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo.

Raoudha Kessentini-Zouari ¹ Jed Jebali ¹ Salma Taboubi ² Najet Srairi-Abid ¹ Maram Morjen ¹ Olfa Kallech-Ziri ¹ Sofiane Bezzine ³ Jacques Marvaldi ² Mohamed El Ayeb ¹ Naziha Marrakchi ^{1, 4} José Luis ^{2, *}

* Corresponding author

1 Institut Pasteur de Tunis

2 CRO2 - Centre de Recherches en Oncologie biologique et Oncopharmacologie

3 CEM Lab - ENIS - Département de Génie Électrique de Sfax [ENIS]

4 Faculté de Médecine de Tunis

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.

Document type :

Journal articles

Domain :

Life Sciences [q-bio] / Genetics

Life Sciences [q-bio] / Biochemistry, Molecular Biology

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https://hal-riip.archives-ouvertes.fr/pasteur-00612150
Contributor : Institut Pasteur Tunis <>
Submitted on : Thursday, July 28, 2011 - 11:23:11 AM
Last modification on : Monday, October 8, 2018 - 5:44:08 PM

CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo.

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CC-PLA2-1 and CC-PLA2-2, two Cerastes cerastes venom-derived phospholipases A2, inhibit angiogenesis both in vitro and in vivo.

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