PARP-1 is involved in autophagy induced by DNA damage
| Autor: | David Martín-Oliva, F. Javier Oliver, Mariano Ruiz de Almodóvar, José Antonio Muñoz-Gámez, José Manuel Rodríguez-Vargas, Antonio Almendros, Rosa Quiles-Pérez, Josiane Ménissier-de Murcia, Gilbert de Murcia, Rocío Aguilar-Quesada |
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| Přispěvatelé: | Biotechnologie et signalisation cellulaire (BSC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS), Université de Strasbourg (UNISTRA)-Institut de recherche de l'Ecole de biotechnologie de Strasbourg (IREBS)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: 3T3 Cells
Cell Apoptosis Quinolones Cathepsin B Autophagy-Related Protein 5 Mice Adenosine Triphosphate MESH: Adenosine Triphosphate MESH: Up-Regulation MESH: Proteins MESH: Animals MESH: Beclin-1 TOR Serine-Threonine Kinases MESH: NAD MESH: 1-Naphthylamine 3T3 Cells Transfection Mitochondria Up-Regulation Cell biology Naphthalimides [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biomolecules [q-bio.BM] 1-Naphthylamine medicine.anatomical_structure MESH: Naphthalimides MESH: Cell Survival PARP inhibitor Beclin-1 Poly(ADP-ribose) Polymerases Microtubule-Associated Proteins Subcellular Fractions Programmed cell death MESH: Enzyme Activation Cell Survival DNA damage MESH: Mitochondria Poly ADP ribose polymerase Poly(ADP-ribose) Polymerase Inhibitors Biology Models Biological MESH: Poly(ADP-ribose) Polymerase Inhibitors Necrosis MESH: Doxorubicin Autophagy medicine Animals MESH: Autophagy [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Molecular Biology MESH: Mice MESH: Protein Kinases MESH: TOR Serine-Threonine Kinases MESH: DNA Damage MESH: Necrosis MESH: Quinolones MESH: Apoptosis Regulatory Proteins MESH: Apoptosis MESH: Poly(ADP-ribose) Polymerases MESH: Models Biological Proteins Cell Biology NAD MESH: Autophagy-Related Protein 5 Enzyme Activation MESH: Microtubule-Associated Proteins Doxorubicin MESH: Gene Deletion MESH: Subcellular Fractions Apoptosis Regulatory Proteins Protein Kinases Gene Deletion DNA Damage |
| Zdroj: | Autophagy Autophagy, Taylor & Francis, 2009, 5 (1), pp.61-74. ⟨10.4161/auto.5.1.7272⟩ |
| ISSN: | 1554-8627 1554-8635 |
| DOI: | 10.4161/auto.5.1.7272⟩ |
| Popis: | Autophagy is a lysosome-dependent degradative pathway frequently activated in tumor cells treated with chemotherapy or radiation. PARP-1 has been implicated in different pathways leading to cell death and its inhibition potentiates chemotherapy-induced cell death. Whether PARP-1 participates in the cell's decision to commit to autophagy following DNA damage is still not known. To address this issue PARP-1 wild-type and deficient cells have been treated with a dose of doxorubicin that induces autophagy. Electron microscopy examination and GFP-LC3 transfection revealed autophagic vesicles and increased expression of genes involved in autophagy (bnip-3, cathepsin b and l and beclin-1) in wild-type cells treated with doxo but not in parp-1(-/-) cells or cells treated with a PARP inhibitor. Mechanistically the lack of autophagic features in PARP-1 deficient/PARP inhibited cells is attributed to prevention of ATP and NAD(+) depletion and to the activation of the key autophagy regulator mTOR. Pharmacological or genetical inhibition of autophagy results in increased cell death, suggesting a protective role of autophagy induced by doxorubicin. These results suggest that autophagy might be cytoprotective during the response to DNA damage and suggest that PARP-1 activation is involved in the cell's decision to undergo autophagy. |
| Databáze: | OpenAIRE |
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