RRC ID 20969
Author Kuwayama H.
Title Arachidonic acid enhances caffeine-induced cell death via caspase-independent cell death.
Journal Sci Rep
Abstract 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. discoideumplaA, which encodes a phospholipase A2 (PLA₂) 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 PLA₂ 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 PLA₂-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.
Volume 2
Pages 577
Published 2012
DOI 10.1038/srep00577
PMID 22896810
PMC PMC3419364
MeSH Apoptosis / drug effects* Apoptosis / genetics Arachidonic Acid / pharmacology* Caffeine / pharmacology* Caspases / metabolism* Cell Survival / drug effects Cyclic AMP / metabolism Dictyostelium / drug effects Dictyostelium / genetics Dictyostelium / metabolism Drug Resistance Drug Synergism Enzyme Activation / drug effects HeLa Cells Humans Phospholipases A2 / metabolism Signal Transduction / drug effects
IF 4.011
Times Cited 2
Cellular slime molds S00141