title: Potential roles of membrane fluidity and ceramide in hyperthermia and alcohol stimulation of TRAIL apoptosis.
abstract: We recently reported that a mild heat shock induces a long lasting stimulation of TRAIL-induced apoptosis of leukemic T-lymphocytes and myeloid cell lines, but not normal T-lymphocytes, which correlates with an enhanced ability of TRAIL to recognize its receptors. As shown here, this phenomenon could be inhibited by the xanthogenate agent D609, a sphingomyelin/ceramide pathway inhibitor. A caspase-dependent and D609-sensitive two-fold increase in ceramide level was elicited by heat shock plus TRAIL combined treatment. One day after heat shock, a similar increase in ceramide was induced by TRAIL. Sphingolipids/ceramides are known to regulate membrane integrity, and heat shock increases membrane fluidity. In this regard, the heat shock plus TRAIL combined treatment resulted in a D609-sensitive membrane fluidization which was far more intense than that induced by heat shock only. We also report that membrane fluidizers, that mimic the effect of heat shock, such benzyl alcohol and ethanol, potently stimulated TRAIL-induced apoptosis. As heat shock, these alcohols increased, in a D609-sensitive manner, membrane fluidity in the presence of TRAIL, the recognition of TRAIL death receptors, and ceramide levels. These results suggest that stress agents that trigger ceramide production and an overall increase in membrane fluidity are stimulators of TRAIL apoptosis.
authors.affiliation: Laboratoire Stress, Chaperons et Mort cellulaire, CNRS UMR 5534, Centre de Génétique Moléculaire et Cellulaire, Université Claude Bernard, Lyon-1, 16 rue Dubois, 69622 Villeurbanne Cedex, France.
authors.forename: Maryline
authors.initials: M
authors.lastname: Moulin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Carpentier
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
authors.forename: André-Patrick
authors.initials: AP
authors.lastname: Arrigo
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019905:Benzyl Alcohol / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D002518:Ceramides / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D018922:HL-60 Cells; D006358:Hot Temperature; D006801:Humans; D007212:Indolizines / Q000494:pharmacology; D019169:Jurkat Cells; D008560:Membrane Fluidity / Q000502:physiology*; D008954:Models, Biological; D009542:Niemann-Pick Diseases / Q000378:metabolism; D009636:Norbornanes; D010627:Phenethylamines / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D013859:Thiocarbamates; D013871:Thiones / Q000494:pharmacology; D020298:U937 Cells
chemical_list: D001952:Bridged-Ring Compounds; D002518:Ceramides; D007212:Indolizines; D009636:Norbornanes; D010627:Phenethylamines; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D013859:Thiocarbamates; D013871:Thiones; D000431:Ethanol; C046498:tricyclodecane-9-yl-xanthogenate; D020169:Caspases; C059901:fantofarone; D019905:Benzyl Alcohol