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Contribution of TMEM16F to pyroptotic cell death

Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X(7) is activated by the noncanonical inflammasome and contributes essentially to pyroptotic...

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Autores principales: Ousingsawat, Jiraporn, Wanitchakool, Podchanart, Schreiber, Rainer, Kunzelmann, Karl
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833444/
https://www.ncbi.nlm.nih.gov/pubmed/29463790
http://dx.doi.org/10.1038/s41419-018-0373-8
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author Ousingsawat, Jiraporn
Wanitchakool, Podchanart
Schreiber, Rainer
Kunzelmann, Karl
author_facet Ousingsawat, Jiraporn
Wanitchakool, Podchanart
Schreiber, Rainer
Kunzelmann, Karl
author_sort Ousingsawat, Jiraporn
collection PubMed
description Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X(7) is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca(2+) activated phospholipid scramblase and ion channel TMEM16F has been shown earlier to control cellular effects downstream of purinergic P2X(7) receptors that ultimately lead to cell death. As pyroptotic cell death is accompanied by an increases in intracellular Ca(2+), we asked whether TMEM16F is activated during pyroptosis. The N-terminal cleavage product of gasdermin D (GD-N) is an executioner of pyroptosis by forming large plasma membrane pores. Expression of GD-N enhanced basal Ca(2+) levels and induced cell death. We observed that GD-N induced cell death in HEK293 and HAP1 cells, which was depending on expression of endogenous TMEM16F. GD-N activated large whole cell currents that were suppressed by knockdown or inhibition of TMEM16F. The results suggest that whole cell currents induced by the pore forming domain of gasdermin-D, are at least in part due to activation of TMEM16F. Knockdown of other TMEM16 paralogues expressed in HAP1 cells suggest TMEM16F as a crucial element during pyroptosis and excluded a role of other TMEM16 proteins. Thus TMEM16F supports pyroptosis and other forms of inflammatory cell death such as ferroptosis. Its potent inhibition by tannic acid may be part of the anti-inflammatory effects of flavonoids.
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spelling pubmed-58334442018-03-06 Contribution of TMEM16F to pyroptotic cell death Ousingsawat, Jiraporn Wanitchakool, Podchanart Schreiber, Rainer Kunzelmann, Karl Cell Death Dis Article Pyroptosis is a highly inflammatory form of programmed cell death that is caused by infection with intracellular pathogens and activation of canonical or noncanonical inflammasomes. The purinergic receptor P2X(7) is activated by the noncanonical inflammasome and contributes essentially to pyroptotic cell death. The Ca(2+) activated phospholipid scramblase and ion channel TMEM16F has been shown earlier to control cellular effects downstream of purinergic P2X(7) receptors that ultimately lead to cell death. As pyroptotic cell death is accompanied by an increases in intracellular Ca(2+), we asked whether TMEM16F is activated during pyroptosis. The N-terminal cleavage product of gasdermin D (GD-N) is an executioner of pyroptosis by forming large plasma membrane pores. Expression of GD-N enhanced basal Ca(2+) levels and induced cell death. We observed that GD-N induced cell death in HEK293 and HAP1 cells, which was depending on expression of endogenous TMEM16F. GD-N activated large whole cell currents that were suppressed by knockdown or inhibition of TMEM16F. The results suggest that whole cell currents induced by the pore forming domain of gasdermin-D, are at least in part due to activation of TMEM16F. Knockdown of other TMEM16 paralogues expressed in HAP1 cells suggest TMEM16F as a crucial element during pyroptosis and excluded a role of other TMEM16 proteins. Thus TMEM16F supports pyroptosis and other forms of inflammatory cell death such as ferroptosis. Its potent inhibition by tannic acid may be part of the anti-inflammatory effects of flavonoids. Nature Publishing Group UK 2018-02-20 /pmc/articles/PMC5833444/ /pubmed/29463790 http://dx.doi.org/10.1038/s41419-018-0373-8 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ousingsawat, Jiraporn
Wanitchakool, Podchanart
Schreiber, Rainer
Kunzelmann, Karl
Contribution of TMEM16F to pyroptotic cell death
title Contribution of TMEM16F to pyroptotic cell death
title_full Contribution of TMEM16F to pyroptotic cell death
title_fullStr Contribution of TMEM16F to pyroptotic cell death
title_full_unstemmed Contribution of TMEM16F to pyroptotic cell death
title_short Contribution of TMEM16F to pyroptotic cell death
title_sort contribution of tmem16f to pyroptotic cell death
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833444/
https://www.ncbi.nlm.nih.gov/pubmed/29463790
http://dx.doi.org/10.1038/s41419-018-0373-8
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