Anti-angiogenic effect of phospholipases A2 from Scorpio maurus venom glands on Human Umbilical Vein Endothelial Cells. (April 2018)

• Record Type: Journal Article
• Authors: Krayem, Najeh; Abdelkefi-Koubaa, Zaineb; Marrakchi, Naziha; Luis, José; Gargouri, Youssef
• Is Part Of: Toxicon. Volume 145(2018)
• Page Start: 6
• Page End: 14
• Publication Date: 2018-04
• Subjects: Adhesion -- Anti-angiogenic effect -- Invasion -- Heterodimeric phospholipase A2 -- Migration -- Scorpion venom glands; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2018.02.042
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: In a previous study, we purified Sm-PLGV an heterodimeric phospholipase A2, from the venom glands of the Tunisian scorpion Scorpio maurus . This enzyme contains a Long chain, a penta-peptide insertion, which is cut out during the maturation process, followed by a short chain. A disulfide bridge links the two chains. Three recombinant forms of this enzyme were produced in Escherichia coli : rPLA2 (+5) with a penta-peptide insert, rPLA2 (-5) without the penta-peptide, and the Long chain alone without the short one. In the present study, we showed that Sm-PLGV, rPLA2 (+5) and rPLA2 (-5) displayed more potent anti-angiogenic activity in vitro than the recombinant Long chain and the short one obtained by chemical synthesis. These phospholipases A2 inhibited in a dose-dependent manner adhesion, migration and invasion of Human Umbilical Vein Endothelial Cells. Using Matrigel™, we demonstrated that Sm-PLGV, rPLA2 (+5) and rPLA2 (-5) significantly inhibited tubulogensesis. We also showed a clear dissociation between the anti-angiogenic effect of Sm-PLGV and its catalytic activity. Highlights: Sm-PLGV is heterodimeric-secreted phospholipase A2 purified from Scorpio maurus venom glands. Recombinant phospholipases rPLA2 (+5) and rPLA2 (-5) inhibited angiogenesis more than the recombinant Long chain. Sm-PLGV, rPLA2 (+5) and rPLA2 (-5) inhibited HUVEC cells adhesion, migration and invasion. There is a dissociation between the anti-angiogenic effect and the enzymatic activity. Sm-PLGV tridimensional structure was not involved in its anti-angiogenic activity.