BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Downregulation of bcl-xL Is Relevant to UV-induced Apoptosis in Fibroblasts

  • Nakagawa, Yuki (Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University) ;
  • Okada, Seiji (Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University) ;
  • Hatano, Masahiko (Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University) ;
  • Ebara, Masaaki (Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University) ;
  • Saisho, Hiromitsu (Department of Medicine and Clinical Oncology (K1), Graduate School of Medicine, Chiba University) ;
  • Tokuhisa, Takeshi (Department of Developmental Genetics (H2), Graduate School of Medicine, Chiba University)
  • Published : 2002.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Exposure to ultraviolet light (UV) induces apoptosis in mammalian cells, The caspase group of proteases is required for the appotosis. This pathway is initiated by a release of cytochrome c from the mitochondria into the cytosol. Several Bcl-2 family proteins can regulate the release of cytochrome c by stabilizing the mitochondrial membrane. Here we show that expression of the endogenous bcl-xL was strongly downregulated in NIH3T3 cells within 2 h after UV-C irradiation, and that of bax was upregulated from 8 h after irradiation. Apoptosis was induced in more than 50% of the NIH3T3 cells 48 h after irradiation. Constitutive overexpression of bcl-xL in NIH3T3 cells protected the UV-induced apoptosis by preventing the loss of mitochondrial membrane potential and the activation of caspase 9. There results suggest that downregulation of Bcl-xL is relevant to UV-induced apoptosis of tibroblasts.

Keywords

References

  1. Aragane, Y., Kulms, D., Metze, D., Wilkes, G., Poppelmann, B., Luger, T. A and Schwarz, T. (1998) Ultraviolet light induces apoptosis via direct activation of CD95 (Fas/APO-1) independently of its ligand CD95L. J. Cell Biol. 140, 171-182. https://doi.org/10.1083/jcb.140.1.171
  2. Boise, L. H. and Thompson, C. B. (1997) BcJ-x(L) can inhibit apoptosis in cells that have undergone Fas-induced protease activation. Proc. Natl. Acad. Sci. USA 94, 3759-3764 https://doi.org/10.1073/pnas.94.8.3759
  3. Budihardjo, L OliveI', H., Lutter, H., Luo, X. and Wang, X. (1999) Biochemical pathways of caspase activation during apoptosis. Annu. Rev. Cell Dev. Biol. 15, 269-290. https://doi.org/10.1146/annurev.cellbio.15.1.269
  4. Chapman, R. S., Cooper, K. D., De Fabo. E. c., Frederic, J. E., Gelatt, K. N .. Hammond, S. P., Hersey, P., Koren, H. S., Ley, R. D. and Noonan. E (1995) Solar ultraviolet radiation and the risk of infectious disease: summary of a workshop. Photochem. Photohiol. 61, 223-247. https://doi.org/10.1111/j.1751-1097.1995.tb03966.x
  5. De Gruijil, E R., Sterenborg, H. J., Forbes, P. D., Davies, R. E., Cole, C., Kelfkens, G., van Weelden, H., Slaper, H. and van der Leun, J. C. (1993) Wavelength dependence of skin cancer induction by ultraviolet irradiation of albino hairless mice. Cancer Res. 53, 53-60.
  6. De GruijiL ER., van Kranen, H. J. and Mullenders, L. H. E (2001) UV-induced DNA damage, repair, mutation and oncogenic pathways in skin cancer. J. Photochem. Photobiol. B 63, 19-27. https://doi.org/10.1016/S1011-1344(01)00199-3
  7. Derijard, B., Hibi, M., Wu, I. -H., Barrett, T., Su, B., Deng, T., Karin, M. and Davis, R. J. (1994) JlNKI: a protein kinase stimulated by UV light and Ha-Ras that binds and phosphorylates the c-Jun activation domain. Cell 76, 1025-1037. https://doi.org/10.1016/0092-8674(94)90380-8
  8. Duckett, C. S., Li, E, Wang, Y., Tomaselli, K. J., Thompson, C. B. and Arm strong, R. C. (1998) Human lAP-like protein regulates programmed cell death downstream of Bcl-xL and cytochrome C. Mol. Cell Biol. 18, 608-615. https://doi.org/10.1128/MCB.18.1.608
  9. Fisher, G. J., Datta, S. C., Talwar, H. S., Wang, Z. Q., Varani, J., Kang, S. and Voorhees, J. J. (1996) Molecular basis of sun-induced premature skin aging and retinoid antagonism. Nature 379. 335-339. https://doi.org/10.1038/379335a0
  10. Geyer. R. K., Nagasawa, H., Little, J. B. and Maki, C. G. (2000) Role and regulation of p53 during an ultraviolet radiation-induced G1cell cycle arrest. Cell Growth Differ. 11, 149-156
  11. Gottschalk, A. R., Boise, L. H., Thompson, C. B. and Quintans, J. (1994) Identification of immunosuppressant-induced apoptosis in a murine B-cell line and its prevention by hcl-x but not bcl-2. Proc. Natl. Acad. Sci. USA 91, 7350-7354. https://doi.org/10.1073/pnas.91.15.7350
  12. Green, D. R. and Reed, J. C. (1998) Mitochondria and apoptosis. Science 281, 1309-1312. https://doi.org/10.1126/science.281.5381.1309
  13. Herrera, B., Alvarez, A M .. Sanchez, A, Femandez, M., Roncero, C., Benito, M. and Fabregat, I. (2001) Reactive oxygen species (ROS) mediates the mitochondrial-dependent apoptosis induced by transforming growth factor (beta) in fetal hepatocytes. FASEB J. 15, 741-751. https://doi.org/10.1096/fj.00-0267com
  14. Isoherranen, K., Sauroja, I., Jansen, C. and Punnonen, K. (1999) UV irradiation induces downregulation of bcl-2 expression in vitro and vivo. Arch. Dermatol. Res. 291, 212-216. https://doi.org/10.1007/s004030050396
  15. Jacotot, E., Costantini. P., Laboureau, E., Zarnzami, N., Susin, S. A. and Kroemer, G. (1999) Mitochondrial membrane penneabilization during the apoptotic process. Annu. NY Acad. Sci. 887. 18-30. https://doi.org/10.1111/j.1749-6632.1999.tb07919.x
  16. Keogh, S. A., Walczak, H., Bouchier-Hayes, L. and Maartin. S. J. (2000) Failure of bcl-2 to block cytochrome c redistribution during TRAIL-induced apoptosis. FEBS Lett. 471, 93-98. https://doi.org/10.1016/S0014-5793(00)01375-2
  17. Kroemer, G. (1997) The proto-oncogene bcl-2 and its role in regulating apoptosis. Nature Med. 3, 614-620. https://doi.org/10.1038/nm0697-614
  18. Kojima, S., Hatano, M., Okada, S., Fukuda, T., Toyama, Y., Yuasa, S., Ito, H. and Tokuhisa, T. (2001) Testicular germ cell apoptosis in Bcl6-deficient mice. Development 128, 57-65.
  19. Kulms, D., Poppelmann, B., Yarosh, D., Luger, T. A, Krutmann, and Schwarz, T. (1999) Nuelear and cell membrane effects contribute independently to the induction of apoptosis in human cells exposed to UVB radiation. Proc. Natl. Acad. Sci. USA 96, 7974-7979. https://doi.org/10.1073/pnas.96.14.7974
  20. Kulms, D. and Schwarz, T. (2000) Molecular mechanisms of UV-inducedapoptosis. Photodermatol. Photoimmunol. Photomed. 16, 195-201. https://doi.org/10.1034/j.1600-0781.2000.160501.x
  21. Liu, X., Kim, C. N., Yang, J., Jemmerson, R. and Wang, X. (1996) Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86, 147-157. https://doi.org/10.1016/S0092-8674(00)80085-9
  22. Los, M., Wesselborg, S. and Schulze-Osthoff, K. (1999) The role of caspases in development, immunity, and apoptotic signal transduction: lessons from knock out mice. Immunity 10, 629-639. https://doi.org/10.1016/S1074-7613(00)80062-X
  23. Maundrell, K., Antonsson, B., Magnenat, E., Camps, M., Muda, M., Chabert, C., Gillieron, C., Boschert, U., Vial-Knecht, E., Martinou, J. C. and Arkinstall, S. (1997) Bel-2 undergoes phosphorylation by c-Jun N-terminal kinase/stress-activated protein kinases in the presence of the constitutively active GTP-binding protein Racl. J. Biol. Chem. 272, 25238-25242. https://doi.org/10.1074/jbc.272.40.25238
  24. Miyaji, E. N. and Menck, C. F. M. (1998) Human bcl-2 expression delays ultraviolet-induced apoptosis in marsupial cells. Photochem. Photobiol. 68, 719-724. https://doi.org/10.1111/j.1751-1097.1998.tb02535.x
  25. Mizushima, S. and Nagata, S. (1990) pEF-BOS, a powerful mammalian expression vector. Nucleic. Acid Res. 18, 5322. https://doi.org/10.1093/nar/18.17.5322
  26. Negrini, M., Sillini, E., Kozak, C., Tsujimoto, Y. and Croce, C. M.(1987) Molecular analysis of mbcl-2: structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma. Cell 49, 455-463. https://doi.org/10.1016/0092-8674(87)90448-X
  27. Nicoletti, I., Migliorati, G., Pagliacci, M. C., Grignani, F. and Riccardi, C. (1991) A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. lmmunol. Methods 139, 271-279. https://doi.org/10.1016/0022-1759(91)90198-O
  28. Ochs, K. and Kaina, B. (2000) Apoptosis induced by DNA damage 06-methylguanine is Bel-2 and caspase-9/3 regulated and Fas/caspase-8 independent. Cancer Res. 60, 5815-5824.
  29. Okada, S., Zhang, H., Hatano, M. and Tokuhisa, T. (1998) A physiologic role of Bel-xL induced in activated macrophages. J. Immunol. 160, 2590-2596.
  30. Oltvai, Z. N., Milliman, C. L. and Korsmeyer, S. J. (1993) Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 74, 609-619 https://doi.org/10.1016/0092-8674(93)90509-O
  31. Reed, J. C. (1997) Cytochrome c: can't live with it-can't live without it. Cell 91, 559-562. https://doi.org/10.1016/S0092-8674(00)80442-0
  32. Rehemtulla, A, Hamilton, C. A, Chinnaiyan, A M. and Dixit, V. M. (1997) Ultraviolet radiation-induced apoptosis is mediated by activation of CD95(Fas/APO-1). J. Biol. Chem. 272, 25783-25786. https://doi.org/10.1074/jbc.272.41.25783
  33. Shimizu, S., Eguchi, Y., Kosaka, H., Kamiike, W., Matsuda, H. and Tsujimoto, Y. (1995) Prevention of hypoxia-induced cell death by Bel-2 and Bel-xL. Nature 374, 811-813. https://doi.org/10.1038/374811a0
  34. Shiraiwa, N., Inohara, N., Okada, S., Yuzaki, M., Shoji, S. and Ohta, S. (1996) An additional form of rat Bel-x. Bel-xbeta, generated by an unspliced RNA, promotes apoptosis in promyeloid cells. J. Biol. Chem. 271, 13258-13265. https://doi.org/10.1074/jbc.271.22.13258
  35. Stein. B., Rahmsdorf, H. J., Steffen, A., Litfin, M. and Herrlich, P. (1989) UV-induced DNA damage is an intermediate step in UV-induced expression of human immunodeficiency virus type 1, collagenase. c-fos, and metallothionein. Mol. Cell. Biol. 9, 5169-5181. https://doi.org/10.1128/MCB.9.11.5169
  36. Suschek, C. V., Krischel, V., Bruch-Gerharz, D., Berendji, D., Krutmann, J., Kroncke, K. -D. and Kolb-Bachofen, V. (1999) Nitric oxide fully protects against UVA-induced apoptosis in tight correlation with hcl-2 up-regulation. J. BioI. Chem. 274, 6130-6137. https://doi.org/10.1074/jbc.274.10.6130
  37. Thoma, F. (1999) Light and dark in chromatin repair: repair of UV-induced DNA lesions by photolyase and nueleotide excision repair. EMBO J. 18, 6585-6598. https://doi.org/10.1093/emboj/18.23.6585
  38. Thompson, C. B. (1995) Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456-1462. https://doi.org/10.1126/science.7878464
  39. Tournier. C., Hess, P., Yang, D. D., Xu, J., Turner, T. K., Nimnual, A., Bar-Sagi. D., Jones, S. N., Fiavell, R. A and Davis, R. J. (2000) Requirement of JNK for stress-induced activation of the cytochrome c-mediated death pathway. Science 288, 870-874. https://doi.org/10.1126/science.288.5467.870
  40. Vermes, I., Haanen, C., Steffens-Nakken, H. and Reutelingsperger, C. (1995) A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J. Immunol. Methods 184, 39-51. https://doi.org/10.1016/0022-1759(95)00072-I
  41. Vu, C. C., Bonner, C. D. and Cidlowski, J. A. (2001) Differential involvement of initiator caspases in apoptotic volume decrease and potassium efflux during Fas- and UV-induced cell death. J. Biol. Chem. 276. 37602-37611. https://doi.org/10.1074/jbc.M104810200
  42. Yin, X. M., Wang, K., Gross, A., Zhao, Y., Zinkel, S., Klocke, B., Roth, K. A and Korsmeyer, S. J. (1999) Bid-deficient mice are resistant to Fas-induced hepatocellular apoptosis. Nature 400, 886-891. https://doi.org/10.1038/23730
  43. Zarnzami, N., Marchetti, P., Castedo, M., Zanin, C., Vayssiere, C., Petit, P. X. and Kroemer, G. (1995) Reduction in mitochondrial potential constitutes an early irreversible step of programmed Iymphocyte death in vivo. J Exp. Med. 181, 1661-1672. https://doi.org/10.1084/jem.181.5.1661

Cited by

  1. Aven blocks DNA damage-induced apoptosis by stabilising Bcl-xL vol.46, pp.13, 2010, https://doi.org/10.1016/j.ejca.2010.06.011
  2. Bcl6 is required for the IL-4-mediated rescue of the B cells from apoptosis induced by IL-21 vol.110, pp.2, 2007, https://doi.org/10.1016/j.imlet.2007.04.009
  3. Apaf-1 deficiency confers resistance to ultraviolet-induced apoptosis in mouse embryonic fibroblasts by disrupting reactive oxygen species amplification production and mitochondrial pathway vol.52, pp.5, 2012, https://doi.org/10.1016/j.freeradbiomed.2011.11.028
  4. Blood glucose fluctuation affects skin collagen metabolism in the diabetic mouse by inhibiting the mitogen-activated protein kinase and Smad pathways vol.38, pp.5, 2013, https://doi.org/10.1111/ced.12002
  5. In vitro studies on the mechanisms involved in chemoprevention using Calluna vulgaris on vascular endothelial cells exposed to UVB vol.136, 2014, https://doi.org/10.1016/j.jphotobiol.2014.04.018