Targeted Vpr-derived Peptides Reach Mitochondria to Induce Apoptosis of aVb3-Expressing Endothelial Cells
| Autor: | Pierre Rustin, Etienne Jacotot, Dominique Rebouillat, J. Brière, Hervé Lecoeur, Déas O, Deniaud A, Myriam Lassalle, Johan Hoebeke, Lena Edelman, Christine Péchoux, D. Chauvier, Magali Brabant, Roux P, Brenner C, Dupont S, Baux L, Alain Langonne, J. P. Briand, A. Borgne-Sanchez |
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| Přispěvatelé: | Laboratoire de génétique et biologie cellulaire (LGBC), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Theraptosis Research Laboratory, Theraptosis S.A., Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie Dynamique (Plate-Forme) (PFID), Institut Pasteur [Paris], Unité de recherche génomique et physiologie de la lactation (GPL), Institut National de la Recherche Agronomique (INRA), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Génomique et Physiologie de la Lactation (GPL), Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut Pasteur [Paris] (IP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL) |
| Jazyk: | angličtina |
| Rok vydání: | 2006 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Apoptosis MESH: Amino Acid Sequence Mitochondrion APOPTOSE Mitochondrial apoptosis-induced channel MESH: Dose-Response Relationship Drug Mice 0302 clinical medicine MESH: Mitochondrial Membranes ENDOTHELIAL CELLS BIOLOGIE CELLULAIRE MESH: Animals MESH: Endothelial Cells Peptide sequence Inbred BALB C 0303 health sciences Mice Inbred BALB C biology MESH: Peptides Cytochrome c Adenine nucleotide translocator PEPTIDES Cell biology Mitochondria [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] MESH: Integrin alphaVbeta3 MESH: Cell Survival 030220 oncology & carcinogenesis MESH: Permeability Mitochondrial Membranes Mitochondrial fission Drug CELLULAR TRAFFICKING APOPTOSIS Voltage-dependent anion channel MESH: Gene Products vpr MESH: Mitochondria Cell Survival Integrin Molecular Sequence Data MESH: Mice Inbred BALB C PTP Permeability Dose-Response Relationship 03 medical and health sciences Gene Products Animals Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology [INFO]Computer Science [cs] Amino Acid Sequence Molecular Biology MESH: Mice 030304 developmental biology MESH: Molecular Sequence Data MESH: Humans Dose-Response Relationship Drug MESH: Apoptosis Gene Products vpr vpr Cell Biology Integrin alphaVbeta3 biology.protein Lysosomes MESH: Lysosomes |
| Zdroj: | Cell Death and Differentiation Cell Death and Differentiation, Nature Publishing Group, 2006, 14, pp.422-35 Cell Death and Differentiation, Nature Publishing Group, 2007, 14, pp.422-435. ⟨10.1038/sj.cdd.4402018⟩ Cell Death and Differentiation, Nature Publishing Group, 2007, 14 (3), pp.422-35. ⟨10.1038/sj.cdd.4402018⟩ Cell Death and Differentiation, 2007, 14 (3), pp.422-35. ⟨10.1038/sj.cdd.4402018⟩ |
| ISSN: | 1350-9047 1476-5403 |
| DOI: | 10.1038/sj.cdd.4402018⟩ |
| Popis: | International audience; The HIV-1 encoded apoptogenic protein Vpr induces mitochondrial membrane permeabilization (MMP) via interactions with the voltage-dependent anion channel (VDAC) and the adenine nucleotide translocator (ANT). We have designed a peptide, TEAM-VP, composed of two functional domains, one a tumor blood vessel RGD-like 'homing' motif and the other an MMP-inducing sequence derived from Vpr. When added to isolated mitochondria, TEAM-VP interacts with ANT and VDAC, reduces oxygen consumption and overcomes Bcl-2 protection to cause inner and outer MMP. TEAM-VP specifically recognizes cell-surface expressed alpha(V)beta(3) integrins, internalizes, temporarily localizes to lysosomes and progressively co-distributes with the mitochondrial compartment with no sign of lysosomal membrane permeabilization. Finally TEAM-VP reaches mitochondria of angiogenic endothelial cells to induce mitochondrial fission, dissipation of the mitochondrial transmembrane potential (DeltaPsi(m)), cytochrome c release and apoptosis hallmarks. Hence, this chimeric peptide constitutes the first example of a virus-derived mitochondriotoxic compound as a candidate to kill selectively tumor neo-endothelia. |
| Databáze: | OpenAIRE |
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