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Caspases activation in hyperthermia-induced stimulation of TRAIL apoptosis

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Cell Stress and Chaperones Aims and scope

Abstract

In leukemia cells, hyperthermia enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. The phenomenon is caspase-dependent and results in membrane changes leading to an increased recognition of TRAIL death receptors by TRAIL. Because either caspase-2 or an apical proteolytic event has been recently proposed to act as an initiator of the cell death mechanism induced by heat shock, we have investigated the hierarchy of caspase activation in cells exposed to the combined heat shock plus TRAIL treatment. We report here that caspases-2, -3, and -8 were the first caspases to be activated. As expected, caspase-8 is required and indispensable during the initiation of this death signaling. Caspase-2 may also participate in the phenomenon but, in contrast to caspase-8, its presence appears dispensable because its depletion by small interfering RNA is devoid of effects. Our observations also suggest a role of caspase-3 and of a particular cleaved form of this caspase during the early signals of heat shock plus TRAIL-induced apoptosis.

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Abbreviations

TRAIL:

TNF-related apoptosis-inducing ligand

FADD:

Fas-associated death domain

DISC:

death signaling inducing complex

FlipL:

long forms of FADD-like ICE inhibitory protein

TNF:

tumor necrosis factor

Hsp:

heat shock protein

HS:

heat shock

PI:

propidium iodide

siNS:

siRNA nonsilencing sequence

z-VAD-fmk:

z-Val-Ala-Asp-fluoromethylketone

References

  • Allan LA, Clarke PR (2007) Phosphorylation of caspase-9 by CDK1/cyclin B1 protects mitotic cells against apoptosis. Mol Cell 26(2):301–310

    Article  PubMed  CAS  Google Scholar 

  • Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J (1996) Human ICE/CED-3 protease nomenclature. Cell 87:171

    Article  PubMed  CAS  Google Scholar 

  • Bang B, Baadsgaard O, Skov L, Jaattela M (2004) Inhibitors of cysteine cathepsin and calpain do not prevent ultraviolet-B-induced apoptosis in human keratinocytes and HeLa cells. Arch Dermatol Res 296:67–73

    Article  PubMed  CAS  Google Scholar 

  • Beere HM (2004) “The stress of dying”: the role of heat shock proteins in the regulation of apoptosis. J Cell Sci 117:2641–2651

    Article  PubMed  CAS  Google Scholar 

  • Callus BA, Vaux DL (2007) Caspase inhibitors: viral, cellular and chemical. Cell Death Differ 14:73–78

    Article  PubMed  CAS  Google Scholar 

  • Carlile GW, Smith H, Weidman M (2004) Caspase-3 has a non apoptotic function in erythroid maturation. Blood 103:4310–4316

    Article  PubMed  CAS  Google Scholar 

  • Chun HJ, Zheng L, Ahmad M, Wang J, Speirs CK, Siegel R, Dale JK, Puck J, Davis J, Hall CG, Skoda-Smith S, Atkinson P, Straus SE, Lenardo MJ (2002) Pleiotropic defects in lymphocyte activation caused by caspase-8 mutations lead to human immunodeficiency. Nature 419:395–399

    Article  PubMed  CAS  Google Scholar 

  • Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17:2215–2223

    Article  PubMed  CAS  Google Scholar 

  • Ekert PG, Silke J, Vaux DL (1999) Caspase inhibitors. Cell Death Differ 6:1081–1086

    Article  PubMed  CAS  Google Scholar 

  • Fernandes-Alnemri T, Litwack G, Alnemri ES (1994) CPP32, a novel human apoptotic protein with homology to Caenorhabditis elegans cell death protein Ced-3 and mammalian interleukin-1 beta-converting enzyme. J Biol Chem 269:30761–30764

    PubMed  CAS  Google Scholar 

  • Gerner EW, Schneider MJ (1975) Induced thermal resistance in HeLa cells. Nature 256:500–502

    Article  PubMed  CAS  Google Scholar 

  • Han Z, Hendrickson EA, Bremner TA, Wyche JH (1997) A sequential two-step mechanism for the production of the mature p17:p12 form of caspase-3 in vitro. J Biol Chem 272:13432–13436

    Article  PubMed  CAS  Google Scholar 

  • Ho PK, Hawkins CJ (2005) Mammalian initiator apoptotic caspases. FEBS J 272:5436–5453

    Article  PubMed  CAS  Google Scholar 

  • Kampinga HH (2006) Cell biological effects of hyperthermia alone or combined with radiation or drugs: a short introduction to newcomers in the field. Int J Hypertherm 22:191–196

    Article  CAS  Google Scholar 

  • Lassus P, Opitz-Araya X, Lazebnik Y (2002) Requirement for caspase-2 in stress-induced apoptosis before mitochondrial permeabilization. Science 297:1352–1354

    Article  PubMed  CAS  Google Scholar 

  • Lavrik IN, Golks A, Baumann S, Krammer PH (2006) Caspase-2 is activated at the CD95 death-inducing signaling complex in the course of CD95-induced apoptosis. Blood 108:559–565

    Article  PubMed  CAS  Google Scholar 

  • Lavrik IN, Golks A, Krammer PH (2005) Caspases: pharmacological manipulation of cell death. J Clin Invest 115:2665–2672

    Article  PubMed  CAS  Google Scholar 

  • Lindquist S (1986) The heat-shock response. Annu Rev Biochem 55:1151–1191

    Article  PubMed  CAS  Google Scholar 

  • Manero F, Ljubic-Thibal V, Moulin M, Goutagny N, Yvin JC, Arrigo AP (2004) Stimulation of Fas agonistic antibody-mediated apoptosis by heparin-like agents suppresses Hsp27 but not Bcl-2 protective activity. Cell Stress Chaperones 9:150–166

    Article  PubMed  CAS  Google Scholar 

  • Martin CA, Panja A (2002) Cytokine regulation of human intestinal primary epithelial cell susceptibility to Fas-mediated apoptosis. Am J Physiol Gasterointest Liver Physiol 282:G92–G104

    CAS  Google Scholar 

  • Martin SJ, Amarante-Mendes GP, Shi L, Chuang TH, Casiano CA, O’Brien GA, Fitzgerald P, Tan EM, Bokoch GM, Greenberg AH, Green DR (1996) The cytotoxic cell protease granzyme B initiates apoptosis in a cell-free system by proteolytic processing and activation of the ICE/CED-3 family protease, CPP32, via a novel two-step mechanism. EMBO J 15:2407–2416

    PubMed  CAS  Google Scholar 

  • Milleron RS, Bratton SB (2006) Heat shock induces apoptosis independently of any known initiator caspase-activating complex. J Biol Chem 281:16991–17000

    Article  PubMed  CAS  Google Scholar 

  • Milleron RS, Bratton SB (2007) ‘Heated’ debates in apoptosis. Cell Mol Life Sci 64:2329–2333

    Article  PubMed  CAS  Google Scholar 

  • Mohr A, Zwacka RM (2007) In situ trapping of initiator caspases reveals intermediate surprises. Cell Biol Int 31:526–530

    Article  PubMed  CAS  Google Scholar 

  • Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–3796

    Article  PubMed  CAS  Google Scholar 

  • Moulin M, Arrigo AP (2006) Long lasting heat shock stimulation of TRAIL-induced apoptosis in transformed T lymphocytes. Exp Cell Res 312:1765–1784

    Article  PubMed  CAS  Google Scholar 

  • Moulin M, Carpentier S, Levade T, Arrigo AP (2007a) Potential roles of membrane fluidity and ceramide up-regulation in the mechanism of hyperthermia- and alcohol-stimulated TRAIL apoptosis. Apoptosis 12:1703–1720

    Article  PubMed  CAS  Google Scholar 

  • Moulin M, Dumontet C, Arrigo AP (2007b) Sensitization of chronic lymphocytic leukemia cells to TRAIL-induced apoptosis by hyperthermia. Cancer Lett 250:117–127

    Article  PubMed  CAS  Google Scholar 

  • Nagy E, Balogi Z, Gombos I, Akerfelt M, Bjorkbom A, Balogh G, Torok Z, Maslyanko A, Fiszer-Kierzkowska A, Lisowska K, Slotte PJ, Sistonen L, Horvath I, Vigh L (2007) Hyperfluidization-coupled membrane microdomain reorganization is linked to activation of the heat shock response in a murine melanoma cell line. Proc Natl Acad Sci U S A 104:7945–7950

    Article  PubMed  CAS  Google Scholar 

  • Shin S, Lee Y, Kim W, Ko H, Choi H, Kim K (2005) Caspase-2 primes cancer cells for TRAIL-mediated apoptosis by processing procaspase-8. EMBO J 24:3532–3542

    Article  PubMed  CAS  Google Scholar 

  • Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J et al (1992) A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768–774

    Article  PubMed  CAS  Google Scholar 

  • Timmer JC, Salvesen GS (2007) Caspase substrates. Cell Death Differ 14:66–72

    Article  PubMed  CAS  Google Scholar 

  • Tinel A, Tschopp J (2004) The PIDDosome, a protein complex implicated in activation of caspase-2 in response to genotoxic stress. Science 304:843–846

    Article  PubMed  CAS  Google Scholar 

  • Tu S, McStay GP, Boucher LM, Mak T, Beere HM, Green DR (2006) In situ trapping of activated initiator caspases reveals a role for caspase-2 in heat shock-induced apoptosis. Nat Cell Biol 8:72–77

    Article  PubMed  CAS  Google Scholar 

  • Vigh L, Horvath I, Maresca B, Harwood JL (2007) Can the stress protein response be controlled by ‘membrane-lipid therapy’. Trends Biochem Sci 32:357–363

    Article  PubMed  CAS  Google Scholar 

  • Wagner KW, Engels IH, Deveraux QL (2004) Caspase-2 can function upstream of bid cleavage in the trail apoptosis pathway. J Biol Chem 279:35047–35052

    Article  PubMed  CAS  Google Scholar 

  • Walczak H, Krammer PH (2000) The CD95 (APO-1/Fas) and the TRAIL (APO-2L) apoptosis systems. Exp Cell Res 256:58–66

    Article  PubMed  CAS  Google Scholar 

  • Wurzer WJ, Planz O, Ehrhardt C, Giner M, Silberzahn T, Pleschka S, Ludwig S (2003) Caspase-3 activation is essential for efficient influenza virus propagation. EMBO J 22:2717–2728

    Article  PubMed  CAS  Google Scholar 

  • Yang S, Thor AD, Edgerton S, Yang X (2006) Caspase-3 mediated feedback activation of apical caspases in doxorubicin and TNF-alpha induced apoptosis. Apoptosis 11:1987–1997

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We would like to thank Dominique Guillet for excellent technical assistance. We wish to thank Dr. Delphine Cuchet (Lyon, France) for helpful advice with the siRNA experiments and for providing control sequence (siNS).

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Authors and Affiliations

  1. 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

    Maryline Moulin & André-Patrick Arrigo

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  1. Maryline Moulin
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  2. André-Patrick Arrigo
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Correspondence to André-Patrick Arrigo.

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Grant support: The Région Rhône-Alpes (Thématique Prioritaire Cancer and Cible 06).

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Moulin, M., Arrigo, AP. Caspases activation in hyperthermia-induced stimulation of TRAIL apoptosis. Cell Stress and Chaperones 13, 313–326 (2008). https://doi.org/10.1007/s12192-008-0027-3

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  • DOI: https://doi.org/10.1007/s12192-008-0027-3

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