Hemilipin, a novel Hemiscorpius lepturus venom heterodimeric phospholipase A2, which inhibits angiogenesis in vitro and in vivo

Abstract : Phospholipases A(2) (PLA(2)) are enzymes which specifically hydrolyze the sn-2 acyl ester bond of phospholipids producing free fatty acids and lysophospholipids. The secreted PLA(2) (sPLA(2)) are the most common types of PLA(2) purified from the snake venom, mammalian pancreatic juice and other sources. They display a variety of toxic actions and biological activities, including antitumoral and antiangiogenic effects. In this study, we report the isolation, characterization and the antiangiogenic activity of Hemilipin, a novel sPLA(2) extracted from Hemiscomius lepturus venom, the most dangerous scorpion in Iran. Hemilipin was purified by HPLC and analyzed by MALDI TOF/MS. The primary structure was determined by EDMAN degradation method and the PLA(2) activity by titration of fatty acids released from the egg yolk phospholipids. Its antiangiogenic activity was studied in vitro by evaluating effects on apoptosis, Matrigel angiogenesis, migration and adhesion of human umbilical vein endothelial cells (HUVECs) and human pulmonary artery endothelial cells (HPAECs) and in vivo by the chorioallantoic membrane (CAM) assay. Mass spectrometry profile showed that Hemilipin is heterodimeric and the PLA(2) test demonstrated its strong hydrolytic activity. N-terminal aminoacid sequence highlighted a significant homology of Hemilipin's small and large subunits with other sPLA(2) group III. Hemilipin had no effect on apoptosis, but strongly impacted angiogenesis both in vitro and in vivo. Our results demonstrate that this novel non toxic sPLA(2) could be a new tool to disrupt at different steps human angiogenesis. (C) 2015 Elsevier Ltd. All rights reserved.
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Toxicon, Elsevier, 2015, 105, pp.34-44. 〈10.1016/j.toxicon.2015.08.022〉
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Contributeur : Institut Pasteur Tunis <>
Soumis le : jeudi 7 septembre 2017 - 12:21:56
Dernière modification le : lundi 8 octobre 2018 - 17:44:08

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Imen Jridi, Ivana Catacchio, Hafed Majdoub, Delavar Shahbazeddah, Mohamed El Ayeb, et al.. Hemilipin, a novel Hemiscorpius lepturus venom heterodimeric phospholipase A2, which inhibits angiogenesis in vitro and in vivo. Toxicon, Elsevier, 2015, 105, pp.34-44. 〈10.1016/j.toxicon.2015.08.022〉. 〈pasteur-01375039〉

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