Role of Protein Kinase C $\delta$ in an Early Stage of Coxsackievirus-B3-Induced Apoptosis in HeLa Cells

  • Rark Jung-Hyun (Department of Biomedical Sciences, National Institute of Health, College of Life Science, Korea University) ;
  • Cho Du-Hyong (Department of Biomedical Sciences, National Institute of Health) ;
  • Yun Cheol-Won (College of Life Science, Korea University) ;
  • Soh Jae-Won (Department of Chemistry, Inha University) ;
  • Jee Young-Mee (Department of Virology, National Institute of Health) ;
  • Park Sang-Ick (Department of Biomedical Sciences, National Institute of Health) ;
  • Jo In-Ho (Department of Biomedical Sciences, National Institute of Health) ;
  • Nam Jae-Hwan (Department of Biotechnology, The Catholic University of Korea)
  • Published : 2006.04.01

Abstract

CVB3 is a virulent human pathogen that induces myocarditis and ultimately dilated cardiomyopathy. Although several apoptotic factors are involved in the cell death induced by CVB3, the upstream signal transduction factors of CVB3-induced apoptosis are still unclear. We explored and characterized the role of PKC $\delta$ in CVB3-infected cells. PKC $\delta$ was cleaved after CVB3 infection and was activated at 6 h postinfection. PKC $\delta$ was also translocated into the nucleus via mitochondria after CVB3 infection, and overexpression of wild-type PKC $\delta$ reduced the apoptotic cell death caused by CVB3. These results indicate that PKC $\delta$ has an antiapoptotic role in CVB3 infection.

Keywords

References

  1. Akita, Y. 2002. Protein kinase C-epsilon (PKC-epsilon): Its unique structure and function. J. Biochem. 132: 847-852 https://doi.org/10.1093/oxfordjournals.jbchem.a003296
  2. Bae, M. A., D. Y. Jun, K. M. Kim, S. K. Kim, J. S. Chun, D. Taub, W. Park, B.-J. Moon, and Y. H. Kim. 2005. Protein tyrosine kinase, $p56^{lck}$ and $p59^{fyn}$, and MAP kinase JNK1 provide an early signal required for upregulation of Fas ligand expression in aburatubolactam C-induced apoptosis of human Jurkat T cells. J. Microbiol. Biotechnol. 15: 756-766
  3. Boshart, M., L. Gissmann, H. Ikenberg, A. Kleinheinz, W. Scheurlen, and H. zur Hausen. 1984. A new type of papillomavirus DNA, its presence in genital cancer biopsies and in cell lines derived from cervical cancer. EMBO J. 3: 1151-1157
  4. Brodie, C. and P. M. Blumberg. 2003. Regulation of cell apoptosis by protein kinase c delta. Apoptosis 8: 19-27 https://doi.org/10.1023/A:1021640817208
  5. Carthy, C. M., B. Yanagawa, H. Luo, D. J. Granville, D. Yang, P. Cheung, C. Cheung, M. Esfandiarei, C. M. Rudin, C. B. Thompson, D. W. Hunt, and B. M. McManus. 2003. Bcl-2 and Bcl-xL overexpression inhibits cytochrome c release, activation of multiple caspases, and virus release following coxsackievirus B3 infection. Virology 313: 147- 157 https://doi.org/10.1016/S0042-6822(03)00242-3
  6. Esfandiarei, M., H. Luo, B. Yanagawa, A. Suarez, D. Dabiri, J. Zhang, and B. M. McManus. 2004. Protein kinase B/Akt regulates coxsackievirus B3 replication through a mechanism which is not caspase dependent. J. Virol. 78: 4289-4298 https://doi.org/10.1128/JVI.78.8.4289-4298.2004
  7. Goldstaub, D., A. Gradi, Z. Bercovitch, Z. Grosmann, Y. Nophar, S. Luria, N. Sonenberg, and C. Kahana. 2000. Poliovirus 2A protease induces apoptotic cell death. Mol. Cell Biol. 4: 1271-1277
  8. Gutcher, I., P. R. Webb, and N. G. Anderson. 2003. The isoform-specific regulation of apoptosis by protein kinase C. Cell Mol. Life Sci. 60: 1061-1070 https://doi.org/10.1007/s00018-003-2281-y
  9. Haleem-Smith, H., E. Y. Chang, Z. Szallasi, P. M. Blumberg, and J. Rivera. 1995. Tyrosine phosphorylation of protein kinase C-delta in response to the activation of the highaffinity receptor for immunoglobulin E modifies its substrate recognition. Proc. Natl. Acad. Sci. USA 92: 9112-9116
  10. Henke, A., H. Launhardt, K. Klement, A. Stelzner, R. Zell, and T. Munder. 2000. Apoptosis in coxsackievirus B3- caused diseases: Interaction between the capsid protein VP2 and the proapoptotic protein siva. J. Virol. 74: 4284-4290 https://doi.org/10.1128/JVI.74.9.4284-4290.2000
  11. Inagaki, K., L. Chen, F. Ikeno, F. H. Lee, K. Imahashi, D. M. Bouley, M. Rezaee, P. G. Yock, E. Murphy, and D. Mochly- Rosen. 2003. Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo. Circulation 108: 2304-2307 https://doi.org/10.1161/01.CIR.0000101682.24138.36
  12. Jun, D. Y., S. W. Rue, B. W. Kim, and Y. H. Kim. 2003. Detection of mitotic centromere-associated kinesin (MCAK) during cell-cycle progression of human Jurkat T cells using polyclonal antibody raised against its N-terminal region overexpressed in E. coli. J. Microbiol. Biotechnol. 13: 912- 918
  13. Kawai, C. 1999. From myocarditis to cardiomyopathy: Mechanism of inflammation and cell death. Circulation 99: 1091-1100 https://doi.org/10.1161/01.CIR.99.8.1091
  14. Kim, H., S.-J. Kim, S.-N. Park, and J.-W. Oh. 2004. Antiviral effect of amphotericin B on Japanese encephalitis virus replication. J. Microbiol. Biotechnol. 14: 121-127 https://doi.org/10.1159/000078104
  15. Koriyama, H., Z. Kouchi, T. Umeda, T. C. Saido, T. Momoi, S. Ishiura, and K. Suzuki. 1999. Proteolytic activation of protein kinase C delta and epsilon by caspase-3 in U937 cells during chemotherapeutic agent-induced apoptosis. Cell. Signal. 11: 831-838 https://doi.org/10.1016/S0898-6568(99)00055-8
  16. Lamphear, B. J., R. Yan, F. Yang, D. Waters, H. D. Liebig, H. Klump, E. Kuechler, T. Skern, and R. E. Rhoads. 1993. Mapping of the cleavage site in protein synthesis initiation factor eIF-4 gamma of the 2A proteases from human Coxsackievirus and rhinovirus. J. Biol. Chem. 268: 19200- 19203
  17. Leverrier, S., A. Vallentin, and D. Joubert. 2002. Positive feedback of protein kinase C proteolytic activation during apoptosis. Biochem. J. 368: 905-913 https://doi.org/10.1042/BJ20021253
  18. Lim, H., M.-K. Kim, Y.-H. Cho, J. M. Kim, Y. Lim, and C.- H. Lee. 2004. Inhibition of cell cycle progression and induction of apoptosis in HeLa cells by HY558-1, a novel CDK inhibitor isolated from Penicillium minioluteum F558. J. Microbiol. Biotechnol. 14: 978-984 https://doi.org/10.1159/000076921
  19. Maisch, B., A. D. Risti, G. Hufnagel, and S. Pankuweit. 2002. Pathophysiology of viral myocarditis: The role of humoral immune response. Cardiovasc. Pathol. 11: 112- 122 https://doi.org/10.1016/S1054-8807(01)00113-2
  20. Meinhardt, G., J. Roth, and G. Totok. 2000. Protein kinase C activation modulates pro- and anti-apoptotic signaling pathways. Eur. J. Cell Biol. 79: 824-833 https://doi.org/10.1078/0171-9335-00100
  21. Murriel, C. L. and D. Mochly-Rosen. 2003. Opposing roles of delta and epsilon PKC in cardiac ischemia and reperfusion: Targeting the apoptotic machinery. Arch. Biochem. Biophys. 420: 246-254 https://doi.org/10.1016/j.abb.2003.08.038
  22. Paroni, G., C. Henderson, C. Schneider, and C. Brancolini. 2002. Caspase-2 can trigger cytochrome C release and apoptosis from the nucleus. J. Biol. Chem. 277: 15147-15161 https://doi.org/10.1074/jbc.M112338200
  23. Soh, J. W., E. H. Lee, R. Prywes, and I. B. Weinstein. 1999. Novel roles of specific isoforms of protein kinase C in activation of the c-fos serum response element. Mol. Cell Biol. 19: 1313-1324 https://doi.org/10.1128/MCB.19.2.1313
  24. Tracy, S., N. M. Chapman, J. Romero, and A. I. Ramsingh. 1996. Genetics of coxsackievirus B cardiovirulence and inflammatory heart muscle disease. Trends Microbiol. 4: 175-179 https://doi.org/10.1016/0966-842X(96)10026-3
  25. Whitton, J. L. 2002. Immunopathology during coxsackievirus infection. Springer Semin. Immunopathol. 24: 201-213 https://doi.org/10.1007/s00281-002-0100-4
  26. Zrachia, A., M. Dobroslav, M. Blass, G. Kazimirsky, I. Kronfeld, P. M. Blumberg, D. Kobiler, S. Lustig, and C. Brodie. 2002. Infection of glioma cells with Sindbis virus induces selective activation and tyrosine phosphorylation of protein kinase C delta. Implications for Sindbis virusinduced apoptosis. J. Biol. Chem. 277: 23693-23701 https://doi.org/10.1074/jbc.M111658200