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The small subunit of Hemilipin2, a new heterodimeric phospholipase A2 from Hemiscorpius lepturus scorpion venom, mediates the antiangiogenic effect of the whole protein.
Jridi, Imen; Catacchio, Ivana; Majdoub, Hafed; Shahbazzadeh, Delavar; El Ayeb, Mohamed; Frassanito, Maria Antonia; Solimando, Antonio Giovanni; Ribatti, Domenico; Vacca, Angelo; Borchani, Lamia.
Afiliación
  • Jridi I; Carthage University, Sciences Faculty of Bizerte, Jarzouna 7021, Bizerte, Tunisia; Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, 13 Place Pasteur, BP 74, Tunis, 1002, Tunisia.
  • Catacchio I; Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, "Aldo Moro" Piazza Giulio Cesare11, I-70124, Bari, Italy.
  • Majdoub H; USCR Protein Sequencer, Faculty of Sciences de Sfax, Route de la Soukra km 4, B.P 802, Sfax 3038, Tunisia.
  • Shahbazzadeh D; Pasteur Institute of Iran, Biotechnology Research Center, Medical Biotechnology Department, Venomics Lab, P.O.Box 131649, Tehran 43551, Iran.
  • El Ayeb M; Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, 13 Place Pasteur, BP 74, Tunis, 1002, Tunisia.
  • Frassanito MA; Department of Biomedical Sciences and Human Oncology, Section of Clinical Pathology, University of Bari Medical School "Aldo Moro", Piazza Giulio Cesare11, I-70124, Bari, Italy.
  • Solimando AG; Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, "Aldo Moro" Piazza Giulio Cesare11, I-70124, Bari, Italy.
  • Ribatti D; Department of Basic Medical Sciences, Neurosciences and Sensory Organs Section of Human Anatomy and Histology, University of Bari Medical School "Aldo Moro", National Cancer Institute "Giovanni Paolo II", I-70124 Bari, Italy.
  • Vacca A; Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari Medical School, "Aldo Moro" Piazza Giulio Cesare11, I-70124, Bari, Italy.
  • Borchani L; Université de Tunis El Manar, Institut Pasteur de Tunis, Laboratoire des Venins et Biomolécules Thérapeutiques LR11IPT08, 13 Place Pasteur, BP 74, Tunis, 1002, Tunisia. Electronic address: Lamia.borchani@pasteur.rns.tn.
Toxicon ; 126: 38-46, 2017 Feb.
Article en En | MEDLINE | ID: mdl-27940138
In a previous study, we reported the identification of Hemilipin, the first secreted heterodimeric phospholipase A2 (sPLA2) from Hemiscorpius lepturus scorpion venom and demonstrated its effective inhibition of all angiogenesis key steps in vitro and in vivo. Here, we aimed to characterize a second sPLA2, Hemilipin2, from the same venom and to elucidate its antiangiogenic effect. The protein was purified by chromatography separation and analyzed by MALDI/TOF mass spectrometry. Its N terminal amino acid sequence was determined by Edman degradation method and the enzymatic activity by fatty acids release assay. Hemilipin2 antiangiogenic activity was investigated by studying its effect in vitro on adhesion, migration and capillary like tube formation of Human Umbilical Vein Endothelial Cells (HUVECs) and Human Pulmonary Artery Endothelial Cells (HPAECs); and in vivo on the chick embryo chorioallantoic membrane (CAM) assay. Data to be presented show that Hemilipin2 is heterodimeric composed by two subunits: the large one has a molecular weight of 12,866 and the small one of 2461 a.m.u. It has a strong calcium-dependent PLA2 activity and impacts angiogenesis in vitro and in vivo without showing any cytotoxic or apoptotic signs. Its chemical modification with p-Bromophenacyl Bromide abolishes the enzymatic activity without affecting the antiangiogenic effect. Furthermore, it has been proved that Hemilipin2 small subunit was able to inhibit blood vessel formation both in vitro and in vivo. These findings may serve as a starting point for the designing of a new generation of specific inhibitor of human angiogenesis at different steps.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Venenos de Escorpión / Inhibidores de la Angiogénesis / Fosfolipasas A2 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Toxicon Año: 2017 Tipo del documento: Article País de afiliación: Túnez Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Venenos de Escorpión / Inhibidores de la Angiogénesis / Fosfolipasas A2 Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Toxicon Año: 2017 Tipo del documento: Article País de afiliación: Túnez Pais de publicación: Reino Unido