, Volume 12, Issue 9, pp 1703–1720 | Cite as

Potential roles of membrane fluidity and ceramide in hyperthermia and alcohol stimulation of TRAIL apoptosis

  • Maryline Moulin
  • Stéphane Carpentier
  • Thierry Levade
  • André-Patrick Arrigo
Original Paper


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.


TRAIL DR5 Apoptosis Ceramide Heat shock Membrane fluidity 



TNF-related apoptosis inducing ligand


Death receptor


Fas associated death domain


Death inducing signaling complex


Long forms of FADD-like ICE inhibitory protein


Tumor necrosis factor


Heat shock protein


Phosphate buffered saline


Heat shock


Propidium iodide



We would like to thank Dominique Guillet for excellent technical assistance. We are grateful to Henning Walczak (Heidelberg, DKFZ, Germany) for helpful discussions and Valérie Arrigo for critical reading of the manuscript. We thank Dr. Herbert (Sanofi-Aventis, Toulouse, France) for providing SR33557 and John Blenis (Boston, USA) for providing the different Jurkat clones. We wish to thank Dr. Ponsin (UMR 870 INSERM/INSA, Lyon, France) for his valuable suggestions on membrane fluidity and help in the use of the spectrofluopolarimeter. This work was supported by The Région Rhône-Alpes (Thématique Prioritaire Cancer, to A.P.A.) and the Ligue contre le Cancer (to T.L.).


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Maryline Moulin
    • 1
  • Stéphane Carpentier
    • 2
  • Thierry Levade
    • 2
  • André-Patrick Arrigo
    • 1
  1. 1.Laboratoire Stress, Chaperons et Mort cellulaire, CNRS UMR 5534, Centre de Génétique Moléculaire et CellulaireUniversité Claude BernardVilleurbanne CedexFrance
  2. 2.Laboratoire de Biochimie, INSERM U858Institut de Médecine Moléculaire de RangueilToulouse Cedex 4France

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