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Research ArticleCellular and Molecular
Open Access

Aripiprazole Cytotoxicity Coincides with Activation of the Unfolded Protein Response in Human Hepatic Cells

Francesca Forno, Yossi Maatuf, Shatha Boukeileh, Priya Dipta, Mohamed Mahameed, Odai Darawshi, Vitor Ferreira, Patricia Rada, Irma García-Martinez, Einav Gross, Avi Priel, Ángela M. Valverde and Boaz Tirosh
Journal of Pharmacology and Experimental Therapeutics September 2020, 374 (3) 452-461; DOI: https://doi.org/10.1124/jpet.119.264481
Francesca Forno
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Yossi Maatuf
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Shatha Boukeileh
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Priya Dipta
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Mohamed Mahameed
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Odai Darawshi
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Vitor Ferreira
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Patricia Rada
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Irma García-Martinez
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Einav Gross
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Avi Priel
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Ángela M. Valverde
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Boaz Tirosh
Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
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Article Information

vol. 374 no. 3 452-461
DOI 
https://doi.org/10.1124/jpet.119.264481
PubMed 
32554435

Published By 
American Society for Pharmacology and Experimental Therapeutics
Print ISSN 
0022-3565
Online ISSN 
1521-0103
History 
  • Received December 8, 2019
  • Accepted June 8, 2020
  • Published online August 17, 2020.

Article Versions

  • Earlier version (June 17, 2020 - 07:44).
  • Earlier version (June 25, 2020 - 10:15).
  • You are viewing the most recent version of this article.
Copyright & Usage 
Copyright © 2020 by The Author(s) This is an open access article distributed under the CC BY-NC Attribution 4.0 International license.

Author Information

  1. Francesca Forno,
  2. Yossi Maatuf,
  3. Shatha Boukeileh,
  4. Priya Dipta,
  5. Mohamed Mahameed,
  6. Odai Darawshi,
  7. Vitor Ferreira,
  8. Patricia Rada,
  9. Irma García-Martinez,
  10. Einav Gross,
  11. Avi Priel,
  12. Ángela M. Valverde, and
  13. Boaz Tirosh
  1. Institute for Drug Research, School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel (F.F., Y.M., S.B., P.D., M.M., O.D., A.P., B.T.); Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM), Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem), ISCIII, Madrid, Spain (V.F., P.R., I.G.-M., Á.M.V.); and Department of Biochemistry and Molecular Biology, IMRIC, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel (E.G.)
  1. Address correspondence to:
    Boaz Tirosh, The School of Pharmacy, The Hebrew University of Jerusalem, POB 12065, Jerusalem 91120, Israel. E-mail: boazt{at}ekmd.huji.ac.il
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Journal of Pharmacology and Experimental Therapeutics: 374 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 374, Issue 3
1 Sep 2020
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Research ArticleCellular and Molecular

Aripiprazole Induces the UPR in Liver Cells

Francesca Forno, Yossi Maatuf, Shatha Boukeileh, Priya Dipta, Mohamed Mahameed, Odai Darawshi, Vitor Ferreira, Patricia Rada, Irma García-Martinez, Einav Gross, Avi Priel, Ángela M. Valverde and Boaz Tirosh
Journal of Pharmacology and Experimental Therapeutics September 1, 2020, 374 (3) 452-461; DOI: https://doi.org/10.1124/jpet.119.264481

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Research ArticleCellular and Molecular

Aripiprazole Induces the UPR in Liver Cells

Francesca Forno, Yossi Maatuf, Shatha Boukeileh, Priya Dipta, Mohamed Mahameed, Odai Darawshi, Vitor Ferreira, Patricia Rada, Irma García-Martinez, Einav Gross, Avi Priel, Ángela M. Valverde and Boaz Tirosh
Journal of Pharmacology and Experimental Therapeutics September 1, 2020, 374 (3) 452-461; DOI: https://doi.org/10.1124/jpet.119.264481
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