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Dual action of Dooku1 on PIEZO1 channel in human red blood cells
PIEZO1 is a mechanosensitive non-selective cation channel, present in many cell types including Red Blood Cells (RBCs). Together with the Gárdos channel, PIEZO1 forms in RBCs a tandem that participates in the rapid adjustment of the cell volume. The pharmacology allowing functional studies of the ro...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365639/ https://www.ncbi.nlm.nih.gov/pubmed/37492641 http://dx.doi.org/10.3389/fphys.2023.1222983 |
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author | Hatem, Aline Poussereau, Gwendal Gachenot, Martin Pérès, Laurent Bouyer, Guillaume Egée, Stéphane |
author_facet | Hatem, Aline Poussereau, Gwendal Gachenot, Martin Pérès, Laurent Bouyer, Guillaume Egée, Stéphane |
author_sort | Hatem, Aline |
collection | PubMed |
description | PIEZO1 is a mechanosensitive non-selective cation channel, present in many cell types including Red Blood Cells (RBCs). Together with the Gárdos channel, PIEZO1 forms in RBCs a tandem that participates in the rapid adjustment of the cell volume. The pharmacology allowing functional studies of the roles of PIEZO1 has only recently been developed, with Yoda1 as a widely used PIEZO1 agonist. In 2018, Yoda1 analogues were developed, as a step towards an improved understanding of PIEZO1 roles and functions. Among these, Dooku1 was the most promising antagonist of Yoda1-induced effects, without having any ability to activate PIEZO1 channels. Since then, Dooku1 has been used in various cell types to antagonize Yoda1 effects. In the present study using RBCs, Dooku1 shows an apparent IC(50) on Yoda1 effects of 90.7 µM, one order of magnitude above the previously reported data on other cell types. Unexpectedly, it was able, by itself, to produce entry of calcium sufficient to trigger Gárdos channel activation. Moreover, Dooku1 evoked a rise in intracellular sodium concentrations, suggesting that it targets a non-selective cation channel. Dooku1 effects were abolished upon using GsMTx4, a known mechanosensitive channel blocker, indicating that Dooku1 likely targets PIEZO1. Our observations lead to the conclusion that Dooku1 behaves as a PIEZO1 agonist in the RBC membrane, similarly to Yoda1 but with a lower potency. Taken together, these results show that the pharmacology of PIEZO1 in RBCs must be interpreted with care especially due to the unique characteristics of RBC membrane and associated cytoskeleton. |
format | Online Article Text |
id | pubmed-10365639 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103656392023-07-25 Dual action of Dooku1 on PIEZO1 channel in human red blood cells Hatem, Aline Poussereau, Gwendal Gachenot, Martin Pérès, Laurent Bouyer, Guillaume Egée, Stéphane Front Physiol Physiology PIEZO1 is a mechanosensitive non-selective cation channel, present in many cell types including Red Blood Cells (RBCs). Together with the Gárdos channel, PIEZO1 forms in RBCs a tandem that participates in the rapid adjustment of the cell volume. The pharmacology allowing functional studies of the roles of PIEZO1 has only recently been developed, with Yoda1 as a widely used PIEZO1 agonist. In 2018, Yoda1 analogues were developed, as a step towards an improved understanding of PIEZO1 roles and functions. Among these, Dooku1 was the most promising antagonist of Yoda1-induced effects, without having any ability to activate PIEZO1 channels. Since then, Dooku1 has been used in various cell types to antagonize Yoda1 effects. In the present study using RBCs, Dooku1 shows an apparent IC(50) on Yoda1 effects of 90.7 µM, one order of magnitude above the previously reported data on other cell types. Unexpectedly, it was able, by itself, to produce entry of calcium sufficient to trigger Gárdos channel activation. Moreover, Dooku1 evoked a rise in intracellular sodium concentrations, suggesting that it targets a non-selective cation channel. Dooku1 effects were abolished upon using GsMTx4, a known mechanosensitive channel blocker, indicating that Dooku1 likely targets PIEZO1. Our observations lead to the conclusion that Dooku1 behaves as a PIEZO1 agonist in the RBC membrane, similarly to Yoda1 but with a lower potency. Taken together, these results show that the pharmacology of PIEZO1 in RBCs must be interpreted with care especially due to the unique characteristics of RBC membrane and associated cytoskeleton. Frontiers Media S.A. 2023-07-10 /pmc/articles/PMC10365639/ /pubmed/37492641 http://dx.doi.org/10.3389/fphys.2023.1222983 Text en Copyright © 2023 Hatem, Poussereau, Gachenot, Pérès, Bouyer and Egée. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Physiology Hatem, Aline Poussereau, Gwendal Gachenot, Martin Pérès, Laurent Bouyer, Guillaume Egée, Stéphane Dual action of Dooku1 on PIEZO1 channel in human red blood cells |
title | Dual action of Dooku1 on PIEZO1 channel in human red blood cells |
title_full | Dual action of Dooku1 on PIEZO1 channel in human red blood cells |
title_fullStr | Dual action of Dooku1 on PIEZO1 channel in human red blood cells |
title_full_unstemmed | Dual action of Dooku1 on PIEZO1 channel in human red blood cells |
title_short | Dual action of Dooku1 on PIEZO1 channel in human red blood cells |
title_sort | dual action of dooku1 on piezo1 channel in human red blood cells |
topic | Physiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10365639/ https://www.ncbi.nlm.nih.gov/pubmed/37492641 http://dx.doi.org/10.3389/fphys.2023.1222983 |
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