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Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation

Oncogene volume 20, pages 6764–6776 (2001)Cite this article

Abstract

Although activation of protein kinase C (PKC) inhibits apoptosis induced by a variety of stimuli including singlet oxygen, the step at which PKC activation interferes with apoptotic signaling is not well defined. We have shown previously that caspase-8 and p38 mediate singlet oxygen-induced apoptosis in HL-60 cells. In this study, we investigated the influence of PKC on regulation of the caspase and p38 pathways initiated by singlet oxygen. Singlet oxygen induced Fas clustering and subsequent recruitment of FADD and caspase-8. Treatment of cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a PKC activator, did not affect the binding of caspase-8 to the aggregated Fas. Surprisingly, under the same conditions PKC activation was still able to prevent singlet oxygen-induced activation of caspase-8 and block its downstream signaling events including cleavage of Bid and caspase-3, decrease in mitochondrial transmembrane potential and release of cytochrome c from mitochondria. Inhibition of PKC by GF109203 or H7 counteracted the TPA-mediated effects on the cleavage of caspases -3 and -8. However, neither activation nor inhibition of PKC affected p38 phosphorylation. These data indicate that PKC inhibits singlet oxygen-induced apoptosis by blocking activation of caspase-8.

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References

  • Agarwal ML, Clay ME, Harvey EJ, Evans HH, Antunez AR, Oleinick NL . 1991 Cancer Res. 51: 5993–5996

  • Agarwal R, Korman NJ, Mohan RR, Feyes DK, Jawed S, Zaim MT, Mukhtar H . 1996 Photochem. Photobiol. 63: 547–552

  • Ahmad N, Gupta S, Feyes DK, Mukhtar H . 2000 J. Invest. Dermatol. 115: 1041–1046

  • Aragane Y, Kulms D, Metze D, Wilkes G, Poppelmann B, Luger TA, Schwarz T . 1998 J. Cell. Biol. 140: 171–182

  • Araujo H, Danziger N, Cordier J, Glowinski J, Chneiweiss H . 1993 J. Biol. Chem. 268: 5911–5920

  • Ashkenazi A, Dixit VM . 1998 Science 281: 1305–1308

  • Assefa Z, Vantieghem A, Garmyn M, Declercq W, Vandenabeele P, Vandenheede JR, Bouillon R, Merlevede W, Agostinis P . 2000 J. Biol. Chem. 275: 21416–21421

  • Baker A, Kanofsky JR . 1992 Photochem. Photobiol. 55: 523–528

  • Behrens MM, Strasser U, Koh JY, Gwag BJ, Choi DW . 1999 Neuroscience 94: 917–927

  • Boldin MP, Goncharov TM, Goltsev YV, Wallach D . 1996 Cell 85: 803–815

  • Bossy-Wetzel E, Green DR . 1999 J. Biol. Chem. 274: 17484–17490

  • Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM . 1995 Cell 81: 505–512

  • Chinnaiyan AM, Tepper CG, Seldin MF, O'Rourke K, Kischkel FC, Hellbardt S, Krammer PH, Peter ME, Dixit VM . 1996 J. Biol. Chem. 271: 4961–4965

  • Clarke AR, Purdie CA, Harrison DJ, Morris RG, Bird CC, Hooper ML, Wyllie AH . 1993 Nature 362: 849–852

  • Cohen GM . 1997 Biochem. J. 326: 1–16

  • Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalo P, Oriente F, Miele C, Caruso M, Formisano P, Beguinot F . 1999b Oncogene 18: 4409–4415

  • Condorelli G, Vigliotta G, Cafieri A, Trencia A, Andalo P, Oriente F, Miele C, Caruso M, Formisano P, Beguinot F . 1999a Oncogene 18: 4409–4415

  • Cook SA, Sugden PH, Clerk A . 1999 Circ. Res. 85: 940–949

  • Dispersyn G, Nuydens R, Connors R, Borgers M, Geerts H . 1999 Biochim. Biophys. Acta. 1428: 357–371

  • Dong S, Hwang HM, Shi X, Holloway L, Yu H . 2000 Chem. Res. Toxicol. 13: 585–593

  • Dumont A, Hehner SP, Hofmann TG, Ueffing M, Droge W, Schmitz ML . 1999 Oncogene 18: 747–757

  • Faubion WA, Guicciardi ME, Miyoshi H, Bronk SF, Roberts PJ, Svingen PA, Kaufmann SH, Gores GJ . 1999 J. Clin. Invest. 103: 137–145

  • Fernandes-Alnemri T, Armstrong RC, Krebs J, Srinivasula SM, Wang L, Bullrich F, Fritz LC, Trapani JA, Tomaselli KJ, Litwack G, Alnemri ES . 1996 Proc. Natl. Acad. Sci. USA 93: 7464–7469

  • Fujii T, Garcia-Bermejo ML, Bernabo JL, Caamano J, Ohba M, Kuroki T, Li L, Yuspa SH, Kazanietz MG . 2000 J. Biol. Chem. 275: 7574–7582

  • Galan A, Garcia-Bermejo ML, Troyano A, Vilaboa NE, de Blas E, Kazanietz MG, Aller P . 2000 J. Biol. Chem. 275: 11418–11424

  • Gomez-Angelats M, Bortner CD, Cidlowski JA . 2000 J. Biol. Chem. 275: 19609–19619

  • Granville DJ, Jiang H, An MT, Levy JG, McManus BM, Hunt DW . 1999 Br. J. Cancer 79: 95–100

  • Grether-Beck S, Olaizola-Horn S, Schmitt H, Grewe M, Jahnke A, Johnson JP, Briviba K, Sies H, Krutmann J . 1996 Proc. Natl. Acad. Sci. USA 93: 14586–14591

  • He XY, Sikes RA, Thomsen S, Chung LW, Jacques SL . 1994 Photochem. Photobiol. 59: 468–473

  • Henderson BW, Dougherty TJ . 1992 Photochem. Photobiol. 55: 145–157

  • Holmstrom TH, Schmitz I, Soderstrom TS, Poukkula M, Johnson VL, Chow SC, Krammer PH, Eriksson JE . 2000 EMBO. J. 19: 5418–5428

  • Ito T, Deng X, Carr B, May WS . 1997 J. Biol. Chem. 272: 11671–11673

  • Jarvis WD, Fornari Jr FA, Browning JL, Gewirtz DA, Kolesnick RN, Grant S . 1994 J. Biol. Chem. 269: 31685–31692

  • Jun CD, Pae HO, Kwak HJ, Yoo JC, Choi BM, Oh CD, Chun JS, Paik SG, Park YH, Chung HT . 1999 Cell Immunol. 194: 36–46

  • Kessel D, Luo Y, Mathieu P, Reiners JJ . 2000 Photochem. Photobiol. 71: 196–200

  • Kitada S, Zapata JM, Andreeff M, Reed JC . 1999 Br. J. Haematol. 106: 995–1004

  • Kowaltowski AJ, Vercesi AE, Fiskum G . 2000 Cell. Death Differ. 7: 903–910

  • Krutmann J . 2000 J. Dermatol. Sci. 23: Suppl. 1) S22–S26

  • Kwon D, Choi C, Lee J, Kim KO, Kim JD, Kim SJ, Choi IH . 2001 J. Neuroimmunol. 113: 1–9

  • Li H, Zhu H, Xu CJ, Yuan J . 1998 Cell 94: 491–501

  • Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X . 1997 Cell 91: 479–489

  • Lotem J, Cragoe Jr EJ, Sachs L . 1991 Blood 78: 953–960

  • Luo X, Budihardjo I, Zou H, Slaughter C, Wang X . 1998 Cell 94: 481–490

  • Luo Y, Kessel D . 1997 Photochem. Photobiol. 66: 479–483

  • Matsura T, Kai M, Fujii Y, Ito H, Yamada K . 1999 Free Radic. Res. 30: 73–83

  • May WS, Tyler PG, Ito T, Armstrong DK, Qatsha KA, Davidson NE . 1994 J. Biol. Chem. 269: 26865–26870

  • Meinhardt G, Roth J, Totok G . 2000 Eur. J. Cell. Biol. 79: 824–833

  • Micheau O, Solary E, Hammann A, Dimanche-Boitrel MT . 1999 J. Biol. Chem. 274: 7987–7992

  • Morita A, Werfel T, Stege H, Ahrens C, Karmann K, Grewe M, Grether-Beck S, Ruzicka T, Kapp A, Klotz LO, Sies H, Krutmann J . 1997 J. Exp. Med. 186: 1763–1768

  • Muzio M, Chinnaiyan AM, Kischkel FC, O'Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM . 1996 Cell 85: 817–827

  • Obeid LM, Linardic CM, Karolak LA, Hannun YA . 1993 Science 259: 1769–1771

  • Ochsner M . 1997 J. Photochem. Photobiol. B 39: 1–18

  • Pae HO, Yoo JC, Choi BM, Lee EJ, Song YS, Chung HT . 2000 Immunopharmacol. Immunotoxicol. 22: 61–73

  • Rehemtulla A, Hamilton CA, Chinnaiyan AM, Dixit VM . 1997 J. Biol. Chem. 272: 25783–25786

  • Rodriguez-Tarduchy G, Lopez-Rivas A . 1989 Biochem. Biophys. Res. Commun. 164: 1069–1075

  • Ruiz-Ruiz MC, Izquierdo M, de Murcia G, Lopez-Rivas A . 1997 Eur. J. Immunol. 27: 1442–1450

  • Ruvolo PP, Deng X, Carr BK, May WS . 1998a J. Biol. Chem. 273: 25436–25442

  • Ruvolo PP, Deng X, Carr BK, May WS . 1998b J. Biol. Chem. 273: 25436–25442

  • Ryter SW, Tyrrell RM . 1998 Free Radic. Biol. Med. 24: 1520–1534

  • Scaffidi C, Fulda S, Srinivasan A, Friesen C, Li F, Tomaselli KJ, Debatin KM, Krammer PH, Peter ME . 1998 Embo. J. 17: 1675–1687

  • Scaffidi C, Schmitz I, Krammer PH, Peter ME . 1999a J. Biol. Chem. 274: 1541–1548

  • Scaffidi C, Schmitz I, Zha J, Korsmeyer SJ, Krammer PH, Peter ME . 1999b J. Biol. Chem. 274: 22532–22538

  • Shen HM, Yang CF, Ding WX, Liu J, Ong CN . 2001 Free Radic. Biol. Med. 30: 9–21

  • Solary E, Bertrand R, Kohn KW, Pommier Y . 1993 Blood 81: 1359–1368

  • Stennicke HR, Jurgensmeier JM, Shin H, Deveraux Q, Wolf BB, Yang X, Zhou Q, Ellerby HM, Ellerby LM, Bredesen D, Green DR, Reed JC, Froelich CJ, Salvesen GS . 1998 J. Biol. Chem. 273: 27084–27090

  • Stoka V, Turk B, Schendel SL, Kim TH, Cirman T, Snipas SJ, Ellerby LM, Bredesen D, Freeze H, Abrahamson M, Bromme D, Krajewski S, Reed JC, Yin XM, Turk V, Salvesen GS . 2000 J. Biol. Chem. 9: 9

  • Suhara T, Fukuo K, Sugimoto T, Morimoto S, Nakahashi T, Hata S, Shimizu M, Ogihara T . 1998 J. Immunol. 160: 4042–4047

  • Takahashi H, Kobayashi H, Hashimoto Y, Matsuo S, Iizuka H . 1995 J. Invest. Dermatol. 105: 810–815

  • Takano Y, Okudaira M, Harmon BV . 1993 Pathol. Res. Pract. 189: 197–203

  • Umansky V, Ushmorov A, Ratter F, Chlichlia K, Bucur M, Lichtenauer A, Rocha M . 2000 Int. J. Oncol. 16: 109–117

  • Ushmorov A, Ratter F, Lehmann V, Droge W, Schirrmacher V, Umansky V . 1999 Blood 93: 2342–2352

  • Varnes ME, Chiu SM, Xue LY, Oleinick NL . 1999 Biochem. Biophys. Res. Commun. 255: 673–679

  • Vogt M, Bauer MK, Ferrari D, Schulze-Osthoff K . 1998 FEBS Lett. 429: 67–72

  • Webber J, Luo Y, Crilly R, Fromm D, Kessel D . 1996 J. Photochem. Photobiol. B 35: 209–211

  • Weishaupt KR, Gomer CJ, Dougherty TJ . 1976 Cancer Res. 36: 2326–2329

  • Xue L, He J, Oleinick NL . 1999 Cell. Death Differ. 6: 855–864

  • Yabuki M, Tsutsui K, Horton AA, Yoshioka T, Utsumi K . 2000 Free Radic. Res. 32: 507–514

  • Yeh JH, Hsu SC, Han SH, Lai MZ . 1998 J. Exp. Med. 188: 1795–1802

  • Yeh WC, Itie A, Elia AJ, Ng M, Shu HB, Wakeham A, Mirtsos C, Suzuki N, Bonnard M, Goeddel DV, Mak TW . 2000 Immunity 12: 633–642

  • Zaidi SI, Oleinick NL, Zaim MT, Mukhtar H . 1993 Photochem. Photobiol. 58: 771–776

  • Zhuang S, Demirs JT, Kochevar IE . 2000 J. Biol. Chem. 275: 25939–25948

  • Zhuang S, Lynch MC, Kochevar IE . 1998 FEBS Lett. 437: 158–162

  • Zhuang S, Lynch MC, Kochevar IE . 1999 Exp. Cell. Res. 250: 203–212

  • Zhuang S, Simon G . 2000 Am. J. Physiol. Cell. Physiol. 279: C341–351

  • Zou H, Henzel WJ, Liu X, Lutschg A, Wang X . 1997 Cell 90: 405–413

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Acknowledgements

We thank Dr Junying Yuan for providing anti-human Bid antibody and Dr Thomas Flotte and Ms Peggy Sherwood for their assistance. This work was supported by NIH grant GM30755.

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  1. Wellman Laboratories of Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, Massachusetts, USA

    Shougang Zhuang, John T Demirs & Irene E Kochevar

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Correspondence to Irene E Kochevar.

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Zhuang, S., Demirs, J. & Kochevar, I. Protein kinase C inhibits singlet oxygen-induced apoptosis by decreasing caspase-8 activation. Oncogene 20, 6764–6776 (2001). https://doi.org/10.1038/sj.onc.1204867

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