Cargando…
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...
Autor principal: | |
---|---|
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 |
_version_ | 1782240719402958848 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3419364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT kuwayamahidekazu arachidonicacidenhancescaffeineinducedcelldeathviacaspaseindependentcelldeath |