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

Imen Jridi, Ivana Catacchio, Hafed Majdoub, Delavar Shahbazeddah, Mohamed El Ayeb, Maria Antonia Frassanito, Domenico Ribatti, Angelo Vacca, Lamia Borchani

Research output: Contribution to journalArticle

Abstract

Phospholipases A2 (PLA2) are enzymes which specifically hydrolyze the sn-2 acyl ester bond of phospholipids producing free fatty acids and lysophospholipids. The secreted PLA2 (sPLA2) are the most common types of PLA2 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 sPLA2 extracted from Hemiscorpius 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 PLA2 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 PLA2 test demonstrated its strong hydrolytic activity. N-terminal aminoacid sequence highlighted a significant homology of Hemilipin's small and large subunits with other sPLA2 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 sPLA2 could be a new tool to disrupt at different steps human angiogenesis.

Original languageEnglish
Article number5163
Pages (from-to)34-44
Number of pages11
JournalToxicon
Volume105
DOIs
Publication statusPublished - Oct 1 2015

Keywords

  • Angiogenesis
  • Hemiscorpius lepturus
  • Heterodimeric sPLA<inf>2</inf> group III
  • HPAEC
  • HUVEC

ASJC Scopus subject areas

  • Toxicology

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    Jridi, I., Catacchio, I., Majdoub, H., Shahbazeddah, D., El Ayeb, M., Frassanito, M. A., Ribatti, D., Vacca, A., & Borchani, L. (2015). Hemilipin, a novel Hemiscorpius lepturus venom heterodimeric phospholipase A2, which inhibits angiogenesis in vitro and in vivo. Toxicon, 105, 34-44. [5163]. https://doi.org/10.1016/j.toxicon.2015.08.022