Advertisement

Apoptosis

, 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

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.

Keywords

TRAIL DR5 Apoptosis Ceramide Heat shock Membrane fluidity 

Abbreviations

TRAIL

TNF-related apoptosis inducing ligand

DR

Death receptor

FADD

Fas associated death domain

DISC

Death inducing signaling complex

FlipL

Long forms of FADD-like ICE inhibitory protein

TNF

Tumor necrosis factor

Hsp

Heat shock protein

PBS

Phosphate buffered saline

HS

Heat shock

PI

Propidium iodide

Notes

Acknowledgments

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.).

References

  1. 1.
    Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA et al (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682PubMedCrossRefGoogle Scholar
  2. 2.
    Ashkenazi A, Dixit VM (1999) Apoptosis control by death and decoy receptors. Curr Opin Cell Biol 11:255–260PubMedCrossRefGoogle Scholar
  3. 3.
    Peter ME, Scaffidi C, Medema JP, Kischkel F, Krammer PH (1999) The death receptors. Results Probl Cell Differ 23:25–63PubMedGoogle Scholar
  4. 4.
    Kimberley FC, Screaton GR (2004) Following a TRAIL: update on a ligand and its five receptors. Cell Res 14:359–372PubMedCrossRefGoogle Scholar
  5. 5.
    Fulda S, Debatin KM (2004) Exploiting death receptor signaling pathways for tumor therapy. Biochim Biophys Acta 1705:27–41PubMedGoogle Scholar
  6. 6.
    Walczak H, Krammer PH (2000) The CD95 (APO-1/Fas) and the TRAIL (APO-2L) apoptosis systems. Exp Cell Res 256:58–66PubMedCrossRefGoogle Scholar
  7. 7.
    Peter ME, Krammer PH (2003) The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ 10:26–35PubMedCrossRefGoogle Scholar
  8. 8.
    MacFarlane M, Merrison W, Dinsdale D, Cohen GM (2000) Active caspases and cleaved cytokeratins are sequestered into cytoplasmic inclusions in TRAIL-induced apoptosis. J Cell Biol 148:1239–1254PubMedCrossRefGoogle Scholar
  9. 9.
    Zhang L, Fang B (2005) Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther 12:228–237PubMedCrossRefGoogle Scholar
  10. 10.
    Arrigo AP (2005) Heat shock proteins as molecular chaperones. Med Sci (Paris) 21:619–625Google Scholar
  11. 11.
    Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92:1564–1572PubMedCrossRefGoogle Scholar
  12. 12.
    Park HG, Han SI, Oh SY, Kang HS (2005) Cellular responses to mild heat stress. Cell Mol Life Sci 62:10–23PubMedCrossRefGoogle Scholar
  13. 13.
    Carratu L, Franceschelli S, Pardini CL, Kobayashi GS, Horvath I, Vigh L, Maresca B (1996) Membrane lipid perturbation modifies the set point of the temperature of heat shock response in yeast. Proc Natl Acad Sci USA 93:3870–3875PubMedCrossRefGoogle Scholar
  14. 14.
    Horvath I, Glatz A, Varvasovszki V, Torok Z, Pali T, Balogh G, Kovacs E, Nadasdi L, Benko S, Joo F, Vigh L (1998) Membrane physical state controls the signaling mechanism of the heat shock response in Synechocystis PCC 6803: identification of hsp17 as a “fluidity gene”. Proc Natl Acad Sci USA 95:3513–3518PubMedCrossRefGoogle Scholar
  15. 15.
    Shigapova N, Torok Z, Balogh G, Goloubinoff P, Vigh L, Horvath I (2005) Membrane fluidization triggers membrane remodeling which affects the thermotolerance in Escherichia coli. Biochem Biophys Res Commun 328:1216–1223PubMedCrossRefGoogle Scholar
  16. 16.
    Vigh L, Maresca B (2002) Dual role of membranes in heat stress: as thermosensors they modulate the expression of stress genes and, by interacting with stress proteins, re-organize thier own lipid order and functionality. In: Storey KB, Storey JM (eds) In cell and molecular response to stress. Elsevier, Amsterdam, pp 173–188Google Scholar
  17. 17.
    Vigh L, Maresca B, Harwood JL (1998) Does the membrane’s physical state control the expression of heat shock and other genes? Trends Biochem Sci 23:369–374PubMedCrossRefGoogle Scholar
  18. 18.
    Balogh G, Horvath I, Nagy E, Hoyk Z, Benko S, Bensaude O, Vigh L (2005) The hyperfluidization of mammalian cell membranes acts as a signal to initiate the heat shock protein response. Febs J 272:6077–6086PubMedCrossRefGoogle Scholar
  19. 19.
    Jenkins GM (2003) The emerging role for sphingolipids in the eukaryotic heat shock response. Cell Mol Life Sci 60:701–710PubMedCrossRefGoogle Scholar
  20. 20.
    Venkatakrishnan CD, Tewari AK, Moldovan L, Cardounel AJ, Zweier JL, Kuppusamy P, Ilangovan G (2006) Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38MAPK and phosphorylation of small heat shock protein 27. Am J Physiol Heart Circ Physiol 291:2680–2691CrossRefGoogle Scholar
  21. 21.
    Jaattela M, Wissing D, Bauer PA, Li GC (1992) Major heat shock protein hsp70 protects tumor cells from tumor necrosis factor cytotoxicity. Embo J 11:3507–3512PubMedGoogle Scholar
  22. 22.
    Ozoren N, El-Deiry W (2002) Heat shock protects HCT116 and H460 cells from TRAIL-induced apoptosis. Exp Cell Res 281:175–181PubMedCrossRefGoogle Scholar
  23. 23.
    Clemons NJ, Buzzard K, Steel R, Anderson RL (2005) Hsp72 inhibits Fas-mediated apoptosis upstream of the mitochondria in type II cells. J Biol Chem 280:9005–9012PubMedCrossRefGoogle Scholar
  24. 24.
    Kampinga HH, Dynlacht JR, Dikomey E (2004) Mechanism of radiosensitization by hyperthermia (> or = 43 degrees C) as derived from studies with DNA repair defective mutant cell lines. Int J Hyperthermia 20:131–139PubMedCrossRefGoogle Scholar
  25. 25.
    Vertrees RA, Das GC, Popov VL, Coscio AM, Goodwin TJ, Logrono R, Zwischenberger JB, Boor PJ (2005) Synergistic interaction of hyperthermia and Gemcitabine in lung cancer. Cancer Biol Ther 4:1144–1153PubMedCrossRefGoogle Scholar
  26. 26.
    Atallah D, Marsaud V, Radanyi C, Kornprobst M, Rouzier R, Elias D, Renoir JM (2004) Thermal enhancement of oxaliplatin-induced inhibition of cell proliferation and cell cycle progression in human carcinoma cell lines. Int J Hyperthermia 20:405–419PubMedCrossRefGoogle Scholar
  27. 27.
    Piantelli M, Tatone D, Castrilli G, Savini F, Maggiano N, Larocca LM, Ranelletti FO, Natali PG (2001) Quercetin and tamoxifen sensitize human melanoma cells to hyperthermia. Melanoma Res 11:469–476PubMedCrossRefGoogle Scholar
  28. 28.
    Tran SE, Meinander A, Holmstrom TH, Rivero-Muller A, Heiskanen KM, Linnau EK, Courtney MJ, Mosser DD, Sistonen L, Eriksson JE (2003) Heat stress downregulates FLIP and sensitizes cells to Fas receptor-mediated apoptosis. Cell Death Differ 10:1137–1147PubMedCrossRefGoogle Scholar
  29. 29.
    Moulin M, Arrigo AP (2006) Long lasting heat shock stimulation of TRAIL-induced apoptosis in transformed T lymphocytes. Exp Cell Res 312:1765–1784PubMedCrossRefGoogle Scholar
  30. 30.
    Moulin M, Dumontet C, Arrigo AP (2007) Sensitization of chronic lymphocytic leukemia cells to TRAIL-induced apoptosis by hyperthermia. Cancer Lett 250:117–127PubMedCrossRefGoogle Scholar
  31. 31.
    Yoo J, Lee YJ (2007) Effect of hyperthermia on TRAIL-induced apoptotic death in human colon cancer cells: development of a novel strategy for regional therapy. J Cell Biochem 101:619–630PubMedCrossRefGoogle Scholar
  32. 32.
    Pespeni MH, Hodnett M, Abayasiriwardana KS, Roux J, Howard M, Broaddus VC, Pittet JF (2007) Sensitization of mesothelioma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by heat stress via the inhibition of the 3-phosphoinositide-dependent kinase 1/Akt pathway. Cancer Res 67:2865–2871PubMedCrossRefGoogle Scholar
  33. 33.
    Ogretmen B, Hannun YA (2004) Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer 4:604–616PubMedCrossRefGoogle Scholar
  34. 34.
    van Blitterswijk WJ, van der Luit AH, Veldman RJ, Verheij M, Borst J (2003) Ceramide: second messenger or modulator of membrane structure and dynamics? Biochem J 369:199–211PubMedCrossRefGoogle Scholar
  35. 35.
    Wanner R, Peiser M, Wittig B (2004) Keratinocytes rapidly readjust ceramide-sphingomyelin homeostasis and contain a phosphatidylcholine-sphingomyelin transacylase. J Invest Dermatol 122:773–782PubMedCrossRefGoogle Scholar
  36. 36.
    Gulbins E (2003) Regulation of death receptor signaling and apoptosis by ceramide. Pharmacol Res 47:393–399PubMedCrossRefGoogle Scholar
  37. 37.
    Hueber AO (2003) Role of membrane microdomain rafts in TNFR-mediated signal transduction. Cell Death Differ 10:7–9PubMedCrossRefGoogle Scholar
  38. 38.
    Cahuzac N, Baum W, Kirkin V, Conchonaud F, Wawrezinieck L, Marguet D, Janssen O, Zornig M, Hueber AO (2006) Fas ligand is localized to membrane rafts, where it displays increased cell death-inducing activity. Blood 107:2384–2391PubMedCrossRefGoogle Scholar
  39. 39.
    Schutze S, Potthoff K, Machleidt T, Berkovic D, Wiegmann K, Kronke M (1992) TNF activates NF-kappa B by phosphatidylcholine-specific phospholipase C-induced “acidic” sphingomyelin breakdown. Cell 71:765–776PubMedCrossRefGoogle Scholar
  40. 40.
    Luberto C, Hannun YA (1998) Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipase C? J Biol Chem 273:14550–14559PubMedCrossRefGoogle Scholar
  41. 41.
    Levade T, Salvayre R, Bes JC, Nezri M, Douste-Blazy L (1985) New tools for the study of Niemann-Pick disease: analogues of natural substrate and Epstein-Barr virus-transformed lymphoid cell lines. Pediatr Res 19:153–157PubMedCrossRefGoogle Scholar
  42. 42.
    Bielawska A, Perry DK, Hannun YA (2001) Determination of ceramides and diglycerides by the diglyceride kinase assay. Anal Biochem 298:141–150PubMedCrossRefGoogle Scholar
  43. 43.
    Kuhry JG, Duportail G, Bronner C, Laustriat G (1985) Plasma membrane fluidity measurements on whole living cells by fluorescence anisotropy of trimethylammoniumdiphenylhexatriene. Biochim Biophys Acta 845:60–67PubMedCrossRefGoogle Scholar
  44. 44.
    Albouz S, Vanier MT, Hauw JJ, Le Saux F, Boutry JM, Baumann N (1983) Effect of tricyclic antidepressants on sphingomyelinase and other sphingolipid hydrolases in C6 cultured glioma cells. Neurosci Lett 36:311–315PubMedCrossRefGoogle Scholar
  45. 45.
    Brenner B, Ferlinz K, Grassme H, Weller M, Koppenhoefer U, Dichgans J, Sandhoff K, Lang F, Gulbins E (1998) Fas/CD95/Apo-I activates the acidic sphingomyelinase via caspases. Cell Death Differ 5:29–37PubMedCrossRefGoogle Scholar
  46. 46.
    Lacour S, Hammann A, Grazide S, Lagadic-Gossmann D, Athias A, Sergent O, Laurent G, Gambert P, Solary E, Dimanche-Boitrel MT (2004) Cisplatin-induced CD95 redistribution into membrane lipid rafts of HT29 human colon cancer cells. Cancer Res 64:3593–3598PubMedCrossRefGoogle Scholar
  47. 47.
    Ahyayauch H, Requero MA, Alonso A, Bennouna M, Goni FM (2002) Surfactant effects of chlorpromazine and imipramine on lipid bilayers containing sphingomyelin and cholesterol. J Colloid Interface Sci 256:284–289PubMedCrossRefGoogle Scholar
  48. 48.
    Saldeen J, Jaffrezou JP, Welsh N (2000) The acid sphingomyelinase inhibitor SR33557 counteracts TNF-alpha-mediated potentiation of IL-1beta-induced NF-kappaB activation in the insulin-producing cell line Rinm5F. Autoimmunity 32:241–254PubMedCrossRefGoogle Scholar
  49. 49.
    Jaffrezou JP, Chen G, Duran GE, Muller C, Bordier C, Laurent G, Sikic BI, Levade T (1995) Inhibition of lysosomal acid sphingomyelinase by agents which reverse multidrug resistance. Biochim Biophys Acta 1266:1–8PubMedCrossRefGoogle Scholar
  50. 50.
    Scaffidi C, Schmitz I, Krammer PH, Peter ME (1999) The role of c-FLIP in modulation of CD95-induced apoptosis. J Biol Chem 274:1541–1548PubMedCrossRefGoogle Scholar
  51. 51.
    Paterson SJ, Butler KW, Huang P, Labelle J, Smith IC, Schneider H (1972) The effects of alcohols on lipid bilayers: a spin label study. Biochim Biophys Acta 266:597–602PubMedCrossRefGoogle Scholar
  52. 52.
    Li GC, Hahn GM (1978) Ethanol-induced tolerance to heat and to adriamycin. Nature 274:699–701PubMedCrossRefGoogle Scholar
  53. 53.
    Li GC, Shiu EC, Hahn GM (1980) Similarities in cellular inactivation by hyperthermia or by ethanol. Radiat Res 82:257–268PubMedCrossRefGoogle Scholar
  54. 54.
    Amtmann E, Sauer G (1987) Selective killing of tumor cells by xanthates. Cancer Lett 35:237–244PubMedCrossRefGoogle Scholar
  55. 55.
    Zhou D, Lauderback CM, Yu T, Brown SA, Butterfield DA, Thompson JS (2001) D609 inhibits ionizing radiation-induced oxidative damage by acting as a potent antioxidant. J Pharmacol Exp Ther 298:103–109PubMedGoogle Scholar
  56. 56.
    Zhang L, Shimizu S, Tsujimoto Y (2005) Two distinct Fas-activated signaling pathways revealed by an antitumor drug D609. Oncogene 24:2954–2962PubMedCrossRefGoogle Scholar
  57. 57.
    Voelkel-Johnson C, Hannun YA, El-Zawahry A (2005) Resistance to TRAIL is associated with defects in ceramide signaling that can be overcome by exogenous C6-ceramide without requiring down-regulation of cellular FLICE inhibitory protein. Mol Cancer Ther 4:1320–1327PubMedCrossRefGoogle Scholar
  58. 58.
    Dai Q, Liu J, Chen J, Durrant D, McIntyre TM, Lee RM (2004) Mitochondrial ceramide increases in UV-irradiated HeLa cells and is mainly derived from hydrolysis of sphingomyelin. Oncogene 23:3650–3658PubMedCrossRefGoogle Scholar
  59. 59.
    Rouquette-Jazdanian AK, Pelassy C, Breittmayer JP, Aussel C (2007) Full CD3/TCR activation through cholesterol-depleted lipid rafts. Cell Signal 19:1404–1418PubMedCrossRefGoogle Scholar
  60. 60.
    Baritaki S, Apostolakis S, Kanellou P, Dimanche-Boitrel MT, Spandidos DA, Bonavida B (2007) Reversal of tumor resistance to apoptotic stimuli by alteration of membrane fluidity: therapeutic implications. Adv Cancer Res 98:149–190PubMedCrossRefGoogle Scholar
  61. 61.
    Torok Z, Tsvetkova NM, Balogh G, Horvath I, Nagy E, Penzes Z, Hargitai J, Bensaude O, Csermely P, Crowe JH, Maresca B, Vigh L (2003) Heat shock protein coinducers with no effect on protein denaturation specifically modulate the membrane lipid phase. Proc Natl Acad Sci USA 100:3131–3136PubMedCrossRefGoogle Scholar
  62. 62.
    Vigh L, Literati PN, Horvath I, Torok Z, Balogh G, Glatz A, Kovacs E, Boros I, Ferdinandy P, Farkas B, Jaszlits L, Jednakovits A, Koranyi L, Maresca B (1997) Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects. Nat Med 3:1150–1154PubMedCrossRefGoogle Scholar

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

Personalised recommendations