Academic Journal
Identification and characterization of Cardiac Glycosides as senolytic compounds
| العنوان: | Identification and characterization of Cardiac Glycosides as senolytic compounds |
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| المؤلفون: | Triana-Martínez, Francisco, Picallos-Rabina, Pilar, Da Silva-Álvarez, Sabela, Pietrocola, Federico, LLanos, Susana, Rodilla, Verónica, Soprano, Enrica, Pedrosa, Pablo, Ferreirós, Alba, Barradas, Marta, Hernández-González, Fernanda, Lalinde, Marta, Prats, Neus, Bernadó, Cristina, Gonzalez, Patricia, Gómez, María, Ikonomopoulou, Maria P, Fernández-Marcos, Pablo J, García-Caballero, Tomás, Del Pino, Pablo, Arribas, Joaquín, Vidal, Anxo, González-Barcia, Miguel, Serrano Marugan, Manuel, Loza, María I, Domínguez, Eduardo, Collado, Manuel |
| المساهمون: | IMDEA Food Institute, Fundación Ramón Areces, Fundación para la Investigación Biomédica del Hospital Universitario Ramón y Cajal, European Molecular Biology Organization, Ministerio de Economía y Competitividad (España), Unión Europea, Unión Europea. Comisión Europea. European Research Council (ERC), Fundación La Caixa |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2019 |
| المجموعة: | REPISALUD (REPositorio Institucional en SALUD del Instituto de Salud Carlos III - ISCIII) |
| مصطلحات موضوعية: | A549 Cells, Animals, Antibiotics, Antineoplastic, Apoptosis, Bleomycin, Breast Neoplasms, Cardiac Glycosides, Cell Line, Tumor, Cell Membrane, Cellular Senescence, Chondrocytes, Digoxin, Female, Fibroblasts, Humans, Hydrogen-Ion Concentration, Mice, Osteoarthritis, Ouabain, Proscillaridin, Pulmonary Fibrosis, Xenograft Model Antitumor Assays |
| الوصف: | Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification. Senescent cells present a slightly depolarized plasma membrane and higher concentrations of H+, making them more susceptible to the action of CGs. These vulnerabilities can be exploited for therapeutic purposes as evidenced by the in vivo eradication of tumors xenografted in mice after treatment with the combination of a senogenic and a senolytic drug. The senolytic effect of CGs is also effective in the elimination of senescence-induced lung fibrosis. This experimental approach allows the identification of compounds with senolytic activity that could potentially be used to develop effective treatments against age-related diseases. ; We thank Matthias Drosten, Alejo Efeyan and Sean Morrison for plasmids. F.T-M. is a postdoctoral fellow from CONACYT (cvu 268632); P.P. is a predoctoral fellow from Xunta de Galicia; M.C. is a "Miguel Servet II" investigator (CPII16/00015). P.P.-R. receives support from a program by the Deputacion de Coruna (BINV-CS/2019). Work in the laboratory of M.C. is funded by grant RTI2018-095818-B-100 (MCIU/AEI/FEDER, UE). P.J.F.-M. is funded by the IMDEA Food Institute, the Ramon Areces Foundation, (CIVP18A3891), and a Ramon y Cajal Award (MICINN) (RYC-2017-22335). M.P.I. is funded by Talento Modalidad-1 Program Grant, Madrid Regional Government (#2018-T1/BIO-11262). F.P. was funded by a Long Term EMBO Fellowship (ALTF-358-2017) and F.H-G. was funded by the PhD4MD Programme of the IRB, Hospital Clinic and IDIBAPS. Work in the laboratory of M.S. was funded by the IRB and by grants from the Spanish Ministry of Economy co-funded by the European Regional Development Fund (ERDF) ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| Relation: | https://doi.org/10.1038/s41467-019-12888-x.; info:eu_repo/grantAgreement/ES/SAF2013-48256-R; info:eu_repo/grantAgreement/EC/H2020/669622; Nat Commun. 2019;10(1):4731; http://hdl.handle.net/20.500.12105/9318; Nature communications |
| DOI: | 10.1038/s41467-019-12888-x |
| الاتاحة: | https://hdl.handle.net/20.500.12105/9318 https://doi.org/10.1038/s41467-019-12888-x |
| Rights: | http://creativecommons.org/licenses/by-nc-sa/4.0/ ; Atribución-NoComercial-CompartirIgual 4.0 Internacional ; open access |
| رقم الانضمام: | edsbas.F8C0A514 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-019-12888-x |