@misc{10481/110620,
year = {2009},
month = {1},
url = {https://hdl.handle.net/10481/110620},
abstract = {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.},
publisher = {Landes BioSciences},
keywords = {Autophagy},
keywords = {DNA damage},
keywords = {PARP-1},
keywords = {Energy Depletion},
keywords = {Beclin 1},
keywords = {ATG-5},
keywords = {mTOR},
keywords = {Doxorubicin},
title = {PARP-1 is involved in autophagy induced by DNA damage},
doi = {https://doi.org/10.4161/auto.5.1.7272},
author = {Muñoz-Gámez, José Antonio and Rodríguez-Vargas, José Manuel and Quiles-Pérez, Rosa and Aguilar-Quesada, Rocío and MArtín-Oliva, David and de Murcia, Gilbert and Menissier de Murcia, Josiane and Almendros, Antonio and Ruiz de Almodóvar, Mariano and Oliver, F Javier},
}