Liu, J, Sadeh, TT, Lippiat, JD orcid.org/0000-0003-3748-7345 et al. (3 more authors) (2021) Small molecules restore the function of mutant CLC5 associated with Dent disease. Journal of Cellular and Molecular Medicine, 25 (2). pp. 1319-1322. ISSN 1582-1838
Abstract
Dent disease type 1 is caused by mutations in the CLCN5 gene that encodes CLC5, a 2Cl−/H+ exchanger. The CLC5 mutants that have been functionally analysed constitute three major classes based on protein expression, cellular localization and channel function. We tested two small molecules, 4‐phenylbutyrate (4PBA) and its analogue 2‐naphthoxyacetic acid (2‐NOAA), for their effect on mutant CLC5 function and expression by whole‐cell patch‐clamp and Western blot, respectively. The expression and function of non‐Class I CLC5 mutants that have reduced function could be restored by either treatment. Cell viability was reduced in cells treated with 2‐NOAA. 4PBA is a FDA‐approved drug for the treatment of urea cycle disorders and offers a potential therapy for Dent disease.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | 2‐naphthoxyacetic acid (2‐NOAA); 4‐phenylbutyrate (4PBA); CLC5; CLCN5; dent disease |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Biomedical Sciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Dec 2020 11:40 |
Last Modified: | 25 Jul 2022 23:05 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1111/jcmm.16091 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:168664 |