Universitat de Lleida
    • English
    • català
    • español
  • English 
    • English
    • català
    • español
  • Login
Repositori Obert UdL
View Item 
  •   Home
  • Recerca
  • Medicina Experimental
  • Articles publicats (Medicina Experimental)
  • View Item
  •   Home
  • Recerca
  • Medicina Experimental
  • Articles publicats (Medicina Experimental)
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

Voltage-gated calcium channel blockers deregulate macroautophagy in cardiomyocytes

Thumbnail
View/Open
023223.pdf (1.623Mb)
Sol·licita una còpia
Issue date
2015
Author
Pushparaj, Charumathi
Das, Arindam
Purroy, Rosa
Nàger Grifo, Mireia
Herreros Danés, Judit
Pamplona Gras, Reinald
Cantí Nicolás, Carles
Suggested citation
Pushparaj, Charumathi; Das, Arindam; Purroy, Rosa; Nàger Grifo, Mireia; Herreros Danés, Judit; Pamplona Gras, Reinald; Cantí Nicolás, Carles; . (2015) . Voltage-gated calcium channel blockers deregulate macroautophagy in cardiomyocytes. The International Journal of Biochemistry & Cell Biology, 2015, vol. 68, p. 166–175. https://doi.org/10.1016/j.biocel.2015.09.010.
Impact


Web of Science logo    citations in Web of Science

Scopus logo    citations in Scopus

Google Scholar logo  Google Scholar
Share
Export to Mendeley
Metadata
Show full item record
Abstract
Voltage-gated calcium channel blockers are widely used for the management of cardiovascular diseases, however little is known about their effects on cardiac cells in vitro. We challenged neonatal ventricular cardiomyocytes (CMs) with therapeutic L-type and T-type Ca2+ channel blockers (nifedipine and mibefradil, respectively), and measured their effects on cell stress and survival, using fluorescent microscopy, Q-PCR and Western blot. Both nifedipine and mibefradil induced a low-level and partially transient up-regulation of three key mediators of the Unfolded Protein Response (UPR), indicative of endoplasmic (ER) reticulum stress. Furthermore, nifedipine triggered the activation of macroautophagy, as evidenced by increased lipidation of microtubule-associated protein 1 light chain 3 (LC3), decreased levels of polyubiquitin-binding protein p62/SQSTM1 and ubiquitinated protein aggregates, that was followed by cell death. In contrast, mibefradil inhibited CMs constitutive macroautophagy and did not promote cell death. The siRNA-mediated gene silencing approach confirmed the pharmacological findings for T-type channels. We conclude that L-type and T-type Ca2+ channel blockers induce ER stress, which is divergently transduced into macroautophagy induction and inhibition, respectively, with relevance for cell viability. Our work identifies VGCCs as novel regulators of autophagy in the heart muscle and provides new insights into the effects of VGCC blockers on CMs homeostasis, that may underlie both noxious and cardioprotective effects.
URI
http://hdl.handle.net/10459.1/59062
DOI
https://doi.org/10.1016/j.biocel.2015.09.010
Is part of
The International Journal of Biochemistry & Cell Biology, 2015, vol. 68, p. 166–175
European research projects
Collections
  • Articles publicats (IRBLleida) [755]
  • Articles publicats (Ciències Mèdiques Bàsiques) [474]
  • Publicacions de projectes de recerca del Plan Nacional [2182]
  • Articles publicats (Medicina Experimental) [246]
  • Articles publicats (Grup de Recerca en Fisiopatologia Metabòlica) [57]

Related items

Showing items related by title, author, creator and subject.

  • T-type Ca2+ Channels: T for Targetable 

    Crespí Sallán, Marta; Visa, Anna; Shaikh, Soni; Nàger Grifo, Mireia; Herreros Danés, Judit; Cantí Nicolás, Carles (Taylor & Francis, 2018-01-17)
    In the last decade TTCC have been unveiled as key regulators of cancer cells biology and thus have been proposed as chemotherapeutic targets. Indeed in vitro and in vivo studies indicate that TTCC pharmacological blockers ...
  • T-type calcium channels drive migration/invasion in BRAFV600E melanoma cells through Snail1 

    Maiques Carlos, Oscar; Barceló Gómez, Carla; Panosa, Anaïs; Pijuan Marquilles, Jordi; Orgaz, Jose L.; Rodríguez Hernández, Irene; Matas Nadal, Clara; Tell, Gemma; Vilella, Ramón; Fabra, Angels; Puig, Susana; Sanz Moreno, Victoria; Matias-Guiu, Xavier; Cantí Nicolás, Carles; Herreros Danés, Judit; Martí Laborda, Rosa Ma.; Macià Armengol, Anna (Wiley, 2018)
    Melanoma is a malignant tumor derived from melanocytes. Once disseminated, it is usually highly resistant to chemotherapy and is associated with poor prognosis. We have recently reported that T-type calcium channels (TTCCs) ...
  • T-type Cav3.1 channels mediate progression and chemotherapeutic resistance in glioblastoma 

    Visa Pretel, Anna; Crespí Sallán, Marta; Maiques Carlos, Oscar; Alza, Lía; Talavera, Elisabeth; López-Ortega, Ricard; Santacana Espasa, Maria; Herreros Danés, Judit; Cantí Nicolás, Carles (American Association for Cancer Research, 2019)
    T-type Ca2+ channels (TTCC) have been identified as key regulators of cancer cell cycle and survival. In vivo studies in glioblastoma (GBM) murine xenografts have shown that drugs able to block TTCC in vitro (such as ...

Contact Us | Send Feedback | Legal Notice
© 2021 BiD. Universitat de Lleida
Metadata subjected to 
 

 

Browse

All of the repositoryCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

Statistics

View Usage Statistics

D'interès

Política institucional d'accés obertDiposita les teves publicacionsDiposita dades de recercaSuport a la recerca

Contact Us | Send Feedback | Legal Notice
© 2021 BiD. Universitat de Lleida
Metadata subjected to