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Targeted Vpr-derived Peptides Reach Mitochondria to Induce Apoptosis of aVb3-Expressing Endothelial Cells
- Source :
- 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⟩
- Publication Year :
- 2006
- Publisher :
- HAL CCSD, 2006.
-
Abstract
- 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.
- Subjects :
- [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
Subjects
Details
- Language :
- English
- ISSN :
- 13509047 and 14765403
- Database :
- OpenAIRE
- Journal :
- 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⟩
- Accession number :
- edsair.doi.dedup.....31ec6591465dfd12cac26a4238bbf731