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Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death

Caffeine is a globally consumed psychostimulant but can be fatal to cells at overdose exposures. Although caspase-dependent apoptosis plays a role in caffeine-induced cell death, the responsible intracellular signalling cascade remains incompletely understood. The cellular slime mould, Dictyostelium...

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Autor principal: Kuwayama, Hidekazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419364/
https://www.ncbi.nlm.nih.gov/pubmed/22896810
http://dx.doi.org/10.1038/srep00577
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author Kuwayama, Hidekazu
author_facet Kuwayama, Hidekazu
author_sort Kuwayama, Hidekazu
collection PubMed
description Caffeine is a globally consumed psychostimulant but can be fatal to cells at overdose exposures. Although caspase-dependent apoptosis plays a role in caffeine-induced cell death, the responsible intracellular signalling cascade remains incompletely understood. The cellular slime mould, Dictyostelium discoideum, does not possess caspase-dependent apoptotic machinery. Here, we observed that ablation of D. discoideum plaA, which encodes a phospholipase A2 (PLA(2)) homolog, leads to a decreased rate of cell death under high caffeine concentrations and to enhanced cell death with the addition of arachidonic acid. Moreover, the inhibition of PLA(2) activity lead to a recovery of the survival rate in caspase-inhibited Hela cervical carcinoma cells under high caffeine concentrations, indicating that caffeine-induced cell death is enhanced via PLA(2)-dependent signalling. Our results indicate that arachidonic acid may be a general second messenger that negatively regulates caffeine tolerance via a caspase-independent cell death cascade, which leads to multiple effects in eukaryotic cells.
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spelling pubmed-34193642012-08-15 Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death Kuwayama, Hidekazu Sci Rep Article Caffeine is a globally consumed psychostimulant but can be fatal to cells at overdose exposures. Although caspase-dependent apoptosis plays a role in caffeine-induced cell death, the responsible intracellular signalling cascade remains incompletely understood. The cellular slime mould, Dictyostelium discoideum, does not possess caspase-dependent apoptotic machinery. Here, we observed that ablation of D. discoideum plaA, which encodes a phospholipase A2 (PLA(2)) homolog, leads to a decreased rate of cell death under high caffeine concentrations and to enhanced cell death with the addition of arachidonic acid. Moreover, the inhibition of PLA(2) activity lead to a recovery of the survival rate in caspase-inhibited Hela cervical carcinoma cells under high caffeine concentrations, indicating that caffeine-induced cell death is enhanced via PLA(2)-dependent signalling. Our results indicate that arachidonic acid may be a general second messenger that negatively regulates caffeine tolerance via a caspase-independent cell death cascade, which leads to multiple effects in eukaryotic cells. Nature Publishing Group 2012-08-15 /pmc/articles/PMC3419364/ /pubmed/22896810 http://dx.doi.org/10.1038/srep00577 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareALike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
Kuwayama, Hidekazu
Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death
title Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death
title_full Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death
title_fullStr Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death
title_full_unstemmed Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death
title_short Arachidonic Acid Enhances Caffeine-Induced Cell Death via Caspase-Independent Cell Death
title_sort arachidonic acid enhances caffeine-induced cell death via caspase-independent cell death
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419364/
https://www.ncbi.nlm.nih.gov/pubmed/22896810
http://dx.doi.org/10.1038/srep00577
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