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Daunorubicin induces cell death via activation of apoptotic signalling pathway and inactivation of survival pathway in muscle-derived stem cells

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Abstract

Daunorubicin (as well as other anthracyclines) is known to be toxic to heart cells and other cells in organism thus limiting its applicability in human cancer therapy. To investigate possible mechanisms of daunorubicin cytotoxicity, we used stem cell lines derived from adult rabbit skeletal muscle. Recently, we have shown that daunorubicin induces apoptotic cell death in our cell model system and distinctly influences the activity of MAP kinases. Here, we demonstrate that two widely accepted antagonistic signalling pathways namely proapoptotic JNK and prosurvival PI3K/AKT participate in apoptosis. Using the Western blot method, we observed the activation of JNK and phosphorylation of its direct target c-Jun along with inactivation of AKT and its direct target GSK in the course of programmed cell death. By means of small-molecule kinase inhibitors and transfection of cells with the genes of the components of these pathways, c-Jun and AKT, we confirm that JNK signalling pathway is proapoptotic, whereas AKT is antiapoptotic in daunorubicin-induced muscle cells. These findings could contribute to new approaches which will result in less toxicity and fewer side effects that are currently associated with the use of daunorubicin in cancer therapies.

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Abbreviations

AKT:

protein kinase B

GSK:

glycogen synthase kinase

MAPK:

mitogen-activated protein kinase

Myo:

rabbit muscle-derived stem cell lines

WB:

Western blot method

References

  • Adamcová M, Pelouch V, Gersl V, Kaplanová J, Mazurová Y, Simůnek T, Klimtová I, Hrdina R. Protein profiling in daunorubicin-induced cardiomyopathy. Gen Physiol Biophys. 2003;22(3):411–9.

    PubMed  Google Scholar 

  • Andreka P, Zang J, Dougherty C, Slepak TI, Webster KA, Bishopric NH. Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis. Circ Res. 2001;88(3):305–12.

    PubMed  CAS  Google Scholar 

  • Baines CP, Molkentin JD. STRESS signalling pathways that modulate cardiac myocyte apoptosis. J Mol Cell Cardiol. 2005;38(1):47–62.

    Article  PubMed  CAS  Google Scholar 

  • Baltriukiene D, Bironaite D, Imbrasaite A, Bukelskiene V, Kalvelyte A. The role of mitogen-activated protein kinases in hydrogen peroxide-induced myogenic cell apoptosis. Biologija. 2008;54(3):208–11.

    Article  Google Scholar 

  • Barthwal MK, Sathyanarayana P, Kundu CN, Rana B, Pradeep A, Sharma C, Woodgett JR, Rana A. Negative regulation of mixed lineage kinase 3 by protein kinase B/AKT leads to cell survival. J Biol Chem. 2003;278(6):3897–902.

    Article  PubMed  CAS  Google Scholar 

  • Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, Leisten JC, Motiwala A, Pierce S, Satoh Y, Bhagwat SS, Manning AM, Anderson DW. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci USA. 2001;98(24):13681–6.

    Article  PubMed  CAS  Google Scholar 

  • Bironaite D, Imbrasaite A, Stulpinas A, Kalvelyte AV. Modulation of c-Jun expression in leukemic cells undergoing apoptosis after chemotherapeutic treatment. Biologija. 2003;4:47–50.

    Google Scholar 

  • Bironaite D, Baltriukiene D, Uralova N, Stulpinas A, Bukelskiene V, Imbrasaite A, Kalvelyte A. Role of MAP kinases in nitric oxide induced muscle-derived adult stem cell apoptosis. Cell Biol Int. 2009;33(7):711–9.

    Article  PubMed  CAS  Google Scholar 

  • Bogoyevitch MA, Arthur PG. Inhibitors of c-Jun N-terminal kinases: JuNK no more? Biochim Biophys Acta. 2008;1784(1):76–93.

    PubMed  CAS  Google Scholar 

  • Bukelskiene V, Baltriukiene D, Bironaite D, Imbrasaite A, Sirmenis R, Balciunas M, Zurauskas E, Kalvelyte A. Muscle-derived primary stem cell lines for heart repair. Seminars in Cardiology. 2005;11(3):99–105.

    Google Scholar 

  • Cerezo A, Martínez-A C, Lanzarot D, Fischer S, Franke TF, Rebollo A. Role of Akt and c-Jun N-terminal kinase 2 in apoptosis induced by interleukin-4 deprivation. Mol Biol Cell. 1998;9(11):3107–18.

    PubMed  CAS  Google Scholar 

  • Chen YR, Wang X, Templeton D, Davis RJ, Tan TH. The role of c-Jun N-terminal kinase (JNK) in apoptosis induced by ultraviolet C and gamma radiation. Duration of JNK activation may determine cell death and proliferation. J Biol Chem. 1996;271(50):31929–36.

    Article  PubMed  CAS  Google Scholar 

  • Cheng JQ, Lindsley CW, Cheng GZ, Yang H, Nicosia SV. The Akt/PKB pathway: molecular target for cancer drug discovery. Oncogene. 2005;24(50):7482–92.

    Article  PubMed  CAS  Google Scholar 

  • Clerk A, Cole SM, Cullingford TE, Harrison JG, Jormakka M, Valks DM. Regulation of cardiac myocyte cell death. Pharmacol Ther. 2003;97(3):223–61.

    Article  PubMed  CAS  Google Scholar 

  • Damrot J, Helbig L, Roos WP, Barrantes SQ, Kaina B, Fritz G. DNA replication arrest in response to genotoxic stress provokes early activation of stress-activated protein kinases (SAPK/JNK). J Mol Biol. 2009;385(5):1409–21.

    Article  PubMed  CAS  Google Scholar 

  • Daury L, Busson M, Tourkine N, Casas F, Cassar-Malek I, Wrutniak-Cabello C, Castellazzi M, Cabello G. Opposing functions of ATF2 and Fos-like transcription factors in c-Jun-mediated myogenin expression and terminal differentiation of avian myoblasts. Oncogene. 2001;20(55):7998–8008.

    Article  PubMed  CAS  Google Scholar 

  • Demetri GD. Structural reengineering of imatinib to decrease cardiac risk in cancer therapy. J Clin Invest. 2007;117(12):3650–3.

    Article  PubMed  CAS  Google Scholar 

  • Deng X, Xiao L, Lang W, Gao F, Ruvolo P, May Jr WS. Novel role for JNK as a stress-activated Bcl2 kinase. J Biol Chem. 2001;276(26):23681–8.

    Article  PubMed  CAS  Google Scholar 

  • Dickancaite E, Cenas N, Kalvelyte A, Serapiniene N. Toxicity of daunorubicin and naphthoquinones to HL-60 cells: an involvement of oxidative stress. Biochem Mol Biol Int. 1997;41(5):987–94.

    PubMed  CAS  Google Scholar 

  • Dietrich J, Han R, Yang Y, Mayer-Pröschel M, Noble M. CNS progenitor cells and oligodendrocytes are targets of chemotherapeutic agents in vitro and in vivo. J Biol. 2006;5(7):22.

    Article  PubMed  Google Scholar 

  • Dougherty CJ, Kubasiak LA, Prentice H, Andreka P, Bishopric NH, Webster KA. Activation of c-Jun N-terminal kinase promotes survival of cardiac myocytes after oxidative stress. Biochem J. 2002;362(Pt 3):561–71.

    Article  PubMed  CAS  Google Scholar 

  • Engelbrecht AM, Niesler C, Page C, Lochner A. p38 and JNK have distinct regulatory functions on the development of apoptosis during simulated ischaemia and reperfusion in neonatal cardiomyocytes. Basic Res Cardiol. 2004;99(5):338–50.

    Article  PubMed  CAS  Google Scholar 

  • Fan M, Goodwin M, Vu T, Brantley-Finley C, Gaarde WA, Chambers TC. Vinblastine-induced phosphorylation of Bcl-2 and Bcl-XL is mediated by JNK and occurs in parallel with inactivation of the Raf-1/MEK/ERK cascade. J Biol Chem. 2000;275(39):29980–5.

    Article  PubMed  CAS  Google Scholar 

  • Faris M, Latinis KM, Kempiak SJ, Koretzky GA, Nel A. (1998) Stress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter. Mol Cell Biol. 1998;18:5414–24.

    PubMed  CAS  Google Scholar 

  • Force T, Kuida K, Namchuk M, Parang K, Kyriakis JM. Inhibitors of protein kinase signalling pathways: emerging therapies for cardiovascular disease. Circulation. 2004;109(10):1196–205.

    Article  PubMed  CAS  Google Scholar 

  • Force T, Krause DS, Van Etten RA. Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition. Nat Rev Cancer. 2007;7(5):332–44.

    Article  PubMed  CAS  Google Scholar 

  • Franklin RA, McCubrey JA. Kinases: positive and negative regulators of apoptosis. Leukemia. 2000;14(12):2019–34.

    Article  PubMed  CAS  Google Scholar 

  • Garg S, Hofstra L, Reutelingsperger C, Narula J. Apoptosis as a therapeutic target in acutely ischemic myocardium. Curr Opin Cardiol. 2003;18(5):372–7.

    Article  PubMed  Google Scholar 

  • Gerson SL. Drug resistance gene transfer: Stem cell protection and therapeutic efficacy. Exp Hematol. 2000;28(12):1315–24.

    Article  PubMed  CAS  Google Scholar 

  • von Gise A, Lorenz P, Wellbrock C, Hemmings B, Berberich-Siebelt F, Rapp UR, Troppmair J. Apoptosis suppression by Raf-1 and MEK1 requires MEK- and phosphatidylinositol 3-kinase-dependent signals. Mol Cell Biol. 2001;21(7):2324–36.

    Article  Google Scholar 

  • Hannun YA. Apoptosis and the dilemma of cancer chemotherapy. Blood. 1997;89(6):1845–53.

    PubMed  CAS  Google Scholar 

  • Hasselblatt P, Rath M, Komnenovic V, Zatloukal K, Wagner EF. Hepatocyte survival in acute hepatitis is due to c-Jun/AP-1-dependent expression of inducible nitric oxide synthase. Proc Natl Acad Sci USA. 2007;104(43):17105–10.

    Article  PubMed  CAS  Google Scholar 

  • Hers I, Vincent EE, Tavaré JM. Akt signalling in health and disease. Cell Signal. 2011;23(10):1515–27.

    Google Scholar 

  • Hettinger K, Vikhanskaya F, Poh MK, Lee MK, de Belle I, Zhang JT, Reddy SA, Sabapathy K. c-Jun promotes cellular survival by suppression of PTEN. Cell Death Differ. 2007;14(2):218–29.

    Article  PubMed  CAS  Google Scholar 

  • Horbinski C, Chu CT. Kinase signaling cascades in the mitochondrion: a matter of life or death. Free Radic Biol Med. 2005;38(1):2–11.

    Article  PubMed  CAS  Google Scholar 

  • Hussain SA, Rea DW, James ND, Palmer DH. Signal transduction therapy: challenges to clinical trial design. Curr Signal Transduct Ther. 2007;2:21–30.

    Article  CAS  Google Scholar 

  • Ihle NT, Powis G. Inhibitors of phosphatidylinositol-3-kinase in cancer therapy. Mol Aspects Med. 2010;31(2):135–44.

    Article  PubMed  CAS  Google Scholar 

  • Jones EV, Dickman MJ, Whitmarsh AJ. Regulation of p73-mediated apoptosis by c-Jun N-terminal kinase. Biochem J. 2007;405(3):617–23.

    Article  PubMed  CAS  Google Scholar 

  • Kamada H, Nito C, Endo H, Chan PH. Bad as a converging signalling molecule between survival PI3-K/Akt and death JNK in neurons after transient focal cerebral ischemia in rats. J Cereb Blood Flow Metab. 2007;27(3):521–33.

    Article  PubMed  CAS  Google Scholar 

  • Kim AH, Khursigara G, Sun X, Franke TF, Chao MV. Akt phosphorylates and negatively regulates apoptosis signal-regulating kinase 1. Mol Cell Biol. 2001;21(3):893–901.

    Article  PubMed  CAS  Google Scholar 

  • Kim MJ, Lee KH, Lee SJ. Ionizing radiation utilizes c-Jun N-terminal kinase for amplification of mitochondrial apoptotic cell death in human cervical cancer cells. FEBS J. 2008;275(9):2096–108.

    Article  PubMed  CAS  Google Scholar 

  • Konorev EA, Vanamala S, Kalyanaraman B. Differences in doxorubicin-induced apoptotic signalling in adult and immature cardiomyocytes. Free Radic Biol Med. 2008;45(12):1723–8.

    Article  PubMed  CAS  Google Scholar 

  • Laurent G, Jaffrézou JP. Signalling pathways activated by daunorubicin. Blood. 2001;98(4):913–24.

    Article  PubMed  CAS  Google Scholar 

  • Lauricella M, Emanuele S, D'Anneo A, Calvaruso G, Vassallo B, Carlisi D, Portanova P, Vento R, Tesoriere G. JNK and AP-1 mediate apoptosis induced by bortezomib in HepG2 cells via FasL/caspase-8 and mitochondria-dependent pathways. Apoptosis. 2006;11(4):607–25.

    Article  PubMed  CAS  Google Scholar 

  • Lee HY, Oh SH, Suh YA, Baek JH, Papadimitrakopoulou V, Huang S, Hong WK. Response of non-small cell lung cancer cells to the inhibitors of phosphatidylinositol 3-kinase/Akt- and MAPK kinase 4/c-Jun NH2-terminal kinase pathways: an effective therapeutic strategy for lung cancer. Clin Cancer Res. 2005;11(16):6065–74.

    Article  PubMed  CAS  Google Scholar 

  • Le-Niculescu H, Bonfoco E, Kasuya Y, Claret FX, Green DR, Karin M. Withdrawal of survival factors results in activation of the JNK pathway in neuronal cells leading to Fas ligand induction and cell death. Mol Cell Biol. 1999;19(1):751–63.

    PubMed  CAS  Google Scholar 

  • Leppä S, Bohmann D. Diverse functions of JNK signaling and c-Jun in stress response and apoptosis. Oncogene. 1999;18(45):6158–62.

    Article  PubMed  Google Scholar 

  • Leppä S, Eriksson M, Saffrich R, Ansorge W, Bohmann D. Complex functions of AP-1 transcription factors in differentiation and survival of PC12 cells. Mol Cell Biol. 2001;21(13):4369–78.

    Article  PubMed  Google Scholar 

  • Lei K, Nimnual A, Zong WX, Kennedy NJ, Flavell RA, Thompson CB, Bar-Sagi D, Davis RJ. The Bax subfamily of Bcl2-related proteins is essential for apoptotic signal transduction by c-Jun NH(2)-terminal kinase. Mol Cell Biol. 2002;22(13):4929–42.

    Article  PubMed  CAS  Google Scholar 

  • Li YM, Guo YP, Liu Y. Cancer chemotherapy induces cardiotoxicity by targeting cardiac stem cells. J Cell Mol Med. 2010;14(11):2630–2.

    Article  PubMed  Google Scholar 

  • Liebermann DA, Gregory B, Hoffman B. AP-1 (Fos/Jun) transcription factors in hematopoietic differentiation and apoptosis. Int J Oncol. 1998;12(3):685–700.

    PubMed  CAS  Google Scholar 

  • Lin A. Activation of the JNK signalling pathway: breaking the brake on apoptosis. Bioessays. 2003;25(1):17–24.

    Article  PubMed  Google Scholar 

  • Liu J, Lin A. Role of JNK activation in apoptosis: a double-edged sword. Cell Res. 2005;15(1):36–42.

    Article  PubMed  Google Scholar 

  • Liu D, Ou L, Clemenson Jr GD, Chao C, Lutske ME, Zambetti GP, Gage FH, Xu Y. Puma is required for p53-induced depletion of adult stem cells. Nat Cell Biol. 2010;12(10):993–8.

    Article  PubMed  CAS  Google Scholar 

  • Lou H, Danelisen I, Singal PK. Involvement of mitogen-activated protein kinases in adriamycin-induced cardiomyopathy. Am J Physiol Heart Circ Physiol. 2005;288(4):H1925–30.

    Article  PubMed  CAS  Google Scholar 

  • Lu PZ, Lai CY, Chan WH. Caffeine induces cell death via activation of apoptotic signal and inactivation of survival signal in human osteoblasts. Int J Mol Sci. 2008;9(5):698–718.

    Article  PubMed  CAS  Google Scholar 

  • Mansouri A, Ridgway LD, Korapati AL, Zhang Q, Tian L, Wang Y, Siddik ZH, Mills GB, Claret FX. Sustained activation of JNK/p38 MAPK pathways in response to cisplatin leads to Fas ligand induction and cell death in ovarian carcinoma cells. J Biol Chem. 2003;278(21):19245–56.

    Article  PubMed  CAS  Google Scholar 

  • McDonald GT, Sullivan R, Paré GC, Graham CH. Inhibition of phosphatidylinositol 3-kinase promotes tumor cell resistance to chemotherapeutic agents via a mechanism involving delay in cell cycle progression. Exp Cell Res. 2010;316(19):3197–206.

    Article  PubMed  CAS  Google Scholar 

  • Meixner A, Karreth F, Kenner L, Penninger JM, Wagner EF. Jun and JunD-dependent functions in cell proliferation and stress response. Cell Death Differ. 2010;17(9):1409–19.

    Article  PubMed  CAS  Google Scholar 

  • Mercille S, Massie B. Induction of apoptosis in oxygen-deprived cultures of hybridoma cells. Cytotechnology. 1994;15(1–3):117–28.

    Article  PubMed  CAS  Google Scholar 

  • Minamino T, Yujiri T, Papst PJ, Chan ED, Johnson GL, Terada N. MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes. Proc Natl Acad Sci USA. 1999;96(26):15127–32.

    Article  PubMed  CAS  Google Scholar 

  • Minotti G, Menna P, Salvatorelli E, Cairo G, Gianni L. Anthracyclines: molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacol Rev. 2004;56(2):185–229.

    Article  PubMed  CAS  Google Scholar 

  • Nobori K, Ito H, Tamamori-Adachi M, Adachi S, Ono Y, Kawauchi J, Kitajima S, Marumo F, Isobe M. ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: a novel cardioprotective role of ATF3. J Mol Cell Cardiol. 2002;34(10):1387–97.

    Article  PubMed  CAS  Google Scholar 

  • Oh JH, Lee JT, Yang ES, Chang JS, Lee DS, Kim SH, Choi YH, Park JW, Kwon TK. The coffee diterpene kahweol induces apoptosis in human leukemia U937 cells through down-regulation of Akt phosphorylation and activation of JNK. Apoptosis. 2009;14(11):1378–86.

    Article  PubMed  CAS  Google Scholar 

  • Ostrovsky O, Bengal E, Aronheim A. Induction of terminal differentiation by the c-Jun dimerization protein JDP2 in C2 myoblasts and rhabdomyosarcoma cells. J Biol Chem. 2002;277(42):40043–54.

    Article  PubMed  CAS  Google Scholar 

  • Pai VB, Nahata MC. Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf. 2000;22(4):263–302.

    Article  PubMed  CAS  Google Scholar 

  • Pechtelidou A, Beis I, Gaitanaki C. Transient and sustained oxidative stress differentially activate the JNK1/2 pathway and apoptotic phenotype in H9c2 cells. Mol Cell Biochem. 2008;309(1–2):177–89.

    Article  PubMed  CAS  Google Scholar 

  • Popelová O, Sterba M, Simůnek T, Mazurová Y, Guncová I, Hroch M, Adamcová M, Gersl V. Deferiprone does not protect against chronic anthracycline cardiotoxicity in vivo. J Pharmacol Exp Ther. 2008;326(1):259–69.

    Article  PubMed  Google Scholar 

  • Potapova O, Basu S, Mercola D, Holbrook NJ. Protective role for c-Jun in the cellular response to DNA damage. J Biol Chem. 2001;276(30):28546–53.

    Article  PubMed  CAS  Google Scholar 

  • Raivich G. c-Jun expression, activation and function in neural cell death, inflammation and repair. J Neurochem. 2008;107(4):898–906.

    PubMed  CAS  Google Scholar 

  • Ravingerová T, Barancík M, Strnisková M. Mitogen-activated protein kinases: a new therapeutic target in cardiac pathology. Mol Cell Biochem. 2003;247(1–2):127–38.

    Article  PubMed  Google Scholar 

  • Sawyers CL. Rational therapeutic intervention in cancer: kinases as drug targets. Curr Opin Genet Dev. 2002;12(1):111–5.

    Article  PubMed  CAS  Google Scholar 

  • Shao Z, Bhattacharya K, Hsich E, Park L, Walters B, Germann U, Wang YM, Kyriakis J, Mohanlal R, Kuida K, Namchuk M, Salituro F, Yao YM, Hou WM, Chen X, Aronovitz M, Tsichlis PN, Bhattacharya S, Force T, Kilter H. c-Jun N-terminal kinases mediate reactivation of Akt and cardiomyocyte survival after hypoxic injury in vitro and in vivo. Circ Res. 2006;98(1):111–8.

    Article  PubMed  CAS  Google Scholar 

  • Shaulian E, Karin M. AP-1 in cell proliferation and survival. Oncogene. 2001;20(19):2390–400.

    Article  PubMed  CAS  Google Scholar 

  • Shaulian E. AP-1–The Jun proteins: oncogenes or tumor suppressors in disguise? Cell Signal. 2010;22(6):894–9.

    Article  PubMed  CAS  Google Scholar 

  • Shen HM, Liu ZG. JNK signalling pathway is a key modulator in cell death mediated by reactive oxygen and nitrogen species. Free Radic Biol Med. 2006;40(6):928–39.

    Article  PubMed  CAS  Google Scholar 

  • Son YO, Hitron JA, Cheng S, Budhraja A, Zhang Z, Lan Guo N, Lee JC, Shi X. The dual roles of c-Jun NH2-terminal kinase signaling in Cr(VI)-induced apoptosis in JB6 cells. Toxicol Sci. 2011;119(2):335–45.

    Article  PubMed  CAS  Google Scholar 

  • Stulpinas A, Bironaite D, Kalvelyte AV. MAPK signalling in skeletal muscle-derived stem cells after daunorubicin treatment. Biologija. 2008;54(3):216–21.

    Article  Google Scholar 

  • Su HY, Bos TJ, Monteclaro FS, Vogt PK. Jun inhibits myogenic differentiation. Oncogene. 1991;6(10):1759–66.

    PubMed  CAS  Google Scholar 

  • Suvasini R, Somasundaram K. Essential role of PI3-kinase pathway in p53-mediated transcription: implications in cancer chemotherapy. Oncogene. 2010;29(25):3605–18.

    Article  PubMed  CAS  Google Scholar 

  • Tekin D, Xi L, Zhao T, Tejero-Taldo MI, Atluri S, Kukreja RC. Mitogen-activated protein kinases mediate heat shock-induced delayed protection in mouse heart. Am J Physiol Heart Circ Physiol. 2001;281(2):H523–32.

    PubMed  CAS  Google Scholar 

  • Toh WH, Siddique MM, Boominathan L, Lin KW, Sabapathy K. c-Jun regulates the stability and activity of the p53 homologue, p73. J Biol Chem. 2004;279(43):44713–22.

    Article  PubMed  CAS  Google Scholar 

  • Tran TH, Andreka P, Rodrigues CO, Webster KA, Bishopric NH. Jun kinase delays caspase-9 activation by interaction with the apoptosome. J Biol Chem. 2007;282(28):20340–50.

    Article  PubMed  CAS  Google Scholar 

  • Varfolomeev EE, Ashkenazi A. Tumor necrosis factor: an apoptosis JuNKie? Cell. 2004;116(4):491–7.

    Article  PubMed  CAS  Google Scholar 

  • Ventura JJ, Hübner A, Zhang C, Flavell RA, Shokat KM, Davis RJ. Chemical genetic analysis of the time course of signal transduction by JNK. Mol Cell. 2006;21(5):701–10.

    Article  PubMed  CAS  Google Scholar 

  • Wei J, Wang W, Chopra I, Li HF, Dougherty CJ, Adi J, Adi N, Wang H, Webster KA. c-Jun N-terminal kinase (JNK-1) confers protection against brief but not extended ischemia during acute myocardial infarction. J Biol Chem. 2011;286(16):13995–4006.

    Article  PubMed  CAS  Google Scholar 

  • Zanotto-Filho A, Gelain DP, Schröder R, Souza LF, Pasquali MA, Klamt F, Moreira JC. The NF kappa B-mediated control of RS and JNK signaling in vitamin A-treated cells: duration of JNK-AP-1 pathway activation may determine cell death or proliferation. Biochem Pharmacol. 2009;77(7):1291–301.

    Article  PubMed  CAS  Google Scholar 

  • Zhang L, Xing D, Liu L, Gao X, Chen M. TNFalpha induces apoptosis through JNK/Bax-dependent pathway in differentiated, but not naïve PC12 cells. Cell Cycle. 2007;6(12):1479–86.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We thank Dr. Jakob Troppmair and Dr. Karin Moelling for the plasmids used in this work. We are also grateful to Lithuanian State Science and Studies Foundation (Grant C-07023) for the initial funding of this work, the Vilnius University Institute of Biochemistry for their services, and Danutė Jakutienė for her excellent technical assistance. The studies of JNK signalling in apoptosis were funded by a grant no. LIG-10034 from the Research Council of Lithuania.

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  1. Vilnius University Institute of Biochemistry, Mokslininkų 12, Vilnius, 08662, Lithuania

    Aurimas Stulpinas, Aušra Imbrasaitė & Audronė Valerija Kalvelytė

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  1. Aurimas Stulpinas
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Correspondence to Aurimas Stulpinas.

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Stulpinas, A., Imbrasaitė, A. & Kalvelytė, A.V. Daunorubicin induces cell death via activation of apoptotic signalling pathway and inactivation of survival pathway in muscle-derived stem cells. Cell Biol Toxicol 28, 103–114 (2012). https://doi.org/10.1007/s10565-011-9210-x

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