Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Cellular and Molecular Biology Letters

Online
ISSN
1689-1392
See all formats and pricing
More options …
Volume 13, Issue 1

Issues

Acidification induces Bax translocation to the mitochondria and promotes ultraviolet light-induced apoptosis

Lin Yang
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yongyu Mei
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Qifeng Xie
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Xiaoyan Han
  • Medical Research Center, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Fucheng Zhang
  • Medical Research Center, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lin Gu
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yufeng Zhang
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Youming Chen
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Gang Li
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Zhiliang Gao
  • Research Unit of Viral Hepatitis, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, P. R. China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2007-10-29 | DOI: https://doi.org/10.2478/s11658-007-0042-x

Abstract

It has been suggested that Bax translocation to the mitochondria is related to apoptosis, and that cytosol acidification contributes to apoptosis events. However, the mechanisms remain obscure. We investigated the effect of acidification on Bax translocation and on ultraviolet (UV) light-induced apoptosis. The Bax translocation assay in vitro showed that Bax translocated to the mitochondria at pH 6.5, whereas no Bax translocation was observed at pH 7.4. VHDBB cells expressing the GFP-Bax fusion protein were treated for 12 h with a pH 6.5 DMEM medium, nigericin (5 μg/ml) and UV light (50 J/cm2), separately or in combination, and Bax translocation to the mitochondria was determined by SDS-PAGE and Western blot, and apoptotic cell death was detected by flow cytometry. The results showed that some of the Bax translocated to the mitochondria in the cells treated with the normal medium, nigericin and UV in combination, whereas all of the Bax translocated to the mitochondria in the cells treated with the pH 6.5 medium, nigericin and UV in combination. In VHDBB cells treated for 12 h with nigericin, UV alone, and UV and nigericin in combination, the respective rates of apoptotic cell death were 25.08%, 33.25% and 52.88%. In cells treated with pH 6.5 medium and nigericin, pH 6.5 medium and UV, and pH 6.5 medium, nigericin and UV in combination, the respective rates of apoptotic cell death increased to 37.19%, 41.42% and 89.44%. Our results indicated that acidification induces Bax translocation from the cytosol to the mitochondria, and promotes UV lightmediated apoptosis. This suggests that there is a possibility of improving cancer treatment by combining acidification with irradiation or chemotherapeutic drugs.

Keywords: Acidification; Bax; Translocation; Ultraviolet light; Apoptosis; Cancer

  • [1] Adams, J.M. and Cory, S. Life-or-death decisions by the Bcl-2 protein family. Trends Biochem. Sci. 26 (2001) 61–66. http://dx.doi.org/10.1016/S0968-0004(00)01740-0CrossrefGoogle Scholar

  • [2] Cory, S. and Adams, J.M. The Bcl2 family: Regulators of the cellular life-ordeath switch. Nat. Rev. 2 (2002) 647–656. http://dx.doi.org/10.1038/nri885CrossrefGoogle Scholar

  • [3] Huang, D. and Strasser, A. BH3-only proteins-essential initiators of apoptotic cell death. Cell 103 (2000) 839–842. http://dx.doi.org/10.1016/S0092-8674(00)00187-2CrossrefGoogle Scholar

  • [4] Wolter, K.G., Hsu, Y.T., Smith, C.L., Nechushtan, A. and Xi, X.G. Movement of bax from the cytosol to mitochondria during apoptosis. J. Cell Biol. 139 (1997) 1281–1292. http://dx.doi.org/10.1083/jcb.139.5.1281CrossrefGoogle Scholar

  • [5] Hsu, Y.T., Wolter, K.G. and Youle, R.J. Cytosol to-membrane redistribution of bax and bcl-xl during apoptosis. Proc. Natl. Acad. Sci. USA 94 (1997) 3668–3672. http://dx.doi.org/10.1073/pnas.94.8.3668CrossrefGoogle Scholar

  • [6] Dejean, L.M., Martinez-Caballero, S., Guo, L., Hughes, C., Teijido, O., Ducret, T., Ichas, F., Korsmeyer, S.J., Antonsson, B., Jonas, E.A. and Kinnally, K.W. Oligomeric Bax is a component of the putative cytochrome c release channel MAC, mitochondrial apoptosis-induced channel. Mol. Biol. Cell 16 (2005) 2424–2432. http://dx.doi.org/10.1091/mbc.E04-12-1111CrossrefGoogle Scholar

  • [7] Hsu, Y.T. and Youle, R.J. Nonionic detergents induce dimerization among members of the bcl-2 family. J. Biol. Chem. 272 (1997) 13829–13834. http://dx.doi.org/10.1074/jbc.272.21.13829CrossrefGoogle Scholar

  • [8] Smaili, S.S., Hsu, Y.T., Sanders, K.M., Russell, J.T. and Youle, R.J. Bax translication to mitochondria subsequent to rapid loss of mitochondrial membrane potential. Cell Death Differ. 8 (2001) 909–920. http://dx.doi.org/10.1038/sj.cdd.4400889CrossrefGoogle Scholar

  • [9] Antonsson, B., Montessuit, S., Sanchez, B. and Martinou, J.C. Bax is presents as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells. J. Biol. Chem. 276 (2001) 1615–1623. http://dx.doi.org/10.1074/jbc.M010810200CrossrefGoogle Scholar

  • [10] Dubrez, L, Coll, J.L., Hurbin, A., Solary, E. and Favrot M.C. Caffeine sensitizes human H358 cell line to p53-mediated apoptosis by inducing mitochondrial translocation and conformational change of BAX protein. J. Biol. Chem. 276 (2001)38980–38987. http://dx.doi.org/10.1074/jbc.M102683200CrossrefGoogle Scholar

  • [11] Gottlieb, R.A., Nordberg, J., Skowronski, E. and Babior, B.M. Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification. Proc. Natl. Acad. Sci. USA 93 (1996) 654–658. http://dx.doi.org/10.1073/pnas.93.2.654CrossrefGoogle Scholar

  • [12] Sala, P.P., Escobar, D.C. and Mollinedo, F. Intracellular alkalinization suppresses lovastation-induced apoptosis in HL-60 cells through the inactivation of a pH-dependent endonuclease. J. Biol. Chem. 270 (1995) 6235–6242. http://dx.doi.org/10.1074/jbc.270.11.6235CrossrefGoogle Scholar

  • [13] Barriere, H., Poujeol, C., Tauc, M. and Blasi, J.M. CFTR modulates programmed cell death by decreasing intracellular pH in Chinese hamaster lung fibroblasts. Am. J. Physiol. Cell Physiol. 281 (2001)C810–824. Google Scholar

  • [14] Barry, M.A., Reynolds, J.E. and Eastman, A. Etoposide-induced apoptosis in human HL-60 cells is associated with intracellular acidification. Cancer Res. 53 (10 Suppl.) (1993) 2349–2357. Google Scholar

  • [15] Goossens, J.F., Henichart, J.P., Dassonneville, L., Facompre, M. and Bailly, C. Relation between intracellular acidification and camptothecin-induced apoptosis in leukemia cells. Eur. J. Pharm. Sci. 10 (2000) 125–131. http://dx.doi.org/10.1016/S0928-0987(99)00091-3CrossrefGoogle Scholar

  • [16] Angoli, D., Delia, D. and Wanke, E. Early cytoplasmic acidification in retinamide-mediatewd apoptosis of human promyelocytic leukemia cells. Biochem. Biophys. Res. Commun. 229 (1996) 681–685. http://dx.doi.org/10.1006/bbrc.1996.1863CrossrefGoogle Scholar

  • [17] Famulski, K.S., Macdonald, D., Paterson, M.C. and Sikora, E. Activation of a low pH-dependent unclease by apoptotic agents. Cell Death Differ. 6 (1999) 281–289. http://dx.doi.org/10.1038/sj.cdd.4400495CrossrefGoogle Scholar

  • [18] Segal, M.S. and Beem, E. Effect of pH, ionic charge, and osmolality on cytochrome c-mediated caspase-3 activity. Am. J. Physiol. Cell Physiol. 281 (2001) C1196–1204. Google Scholar

  • [19] Furlong, I.J., Ascaso, R., Rivas, A.L. and Collins, M.K. Intracellular acidification induces apoptosis by stimulating ICE-like protease. J. Cell Sci. 110 (1997) 653–661. Google Scholar

  • [20] Williams, A.C., Collard, T.J. and Paraskeva, C. An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis. Oncogene 18 (1999) 3199–3204. http://dx.doi.org/10.1038/sj.onc.1202660CrossrefGoogle Scholar

  • [21] Collins, M.K., Furlong, I.J., Malde, P., Ascaso, R. and Oliver, J. An apoptotic endonuclease activated either by decreasing pH or by increasing calcium. J. Cell Sci. 109 (1996) 2393–2399. Google Scholar

  • [22] Juin, P., Hueber, A.O., Littlewood, T. and Evan, G. c-Myc-induced sensitization to apoptosis is mediated through cytochrome c release. Genes Dev. 13 (1999) 1367–1381. CrossrefGoogle Scholar

  • [23] Jia, L., Macey, M.G., Yin, Y., Newland, A.C. and Kelsev, S.M. Subcellular distribution and redistribution of Bcl-2 family proteins in human leukemia cells and undergoing apoptosis. Blood 93 (1999) 2353–2359. Google Scholar

  • [24] Haq, R. and Zanke, B. Inhibition of apoptotic signaling pathways in cancer cells as a mechanism of chemotherapy resistance. Cancer Metastasis Rev. 17 (1998) 233–239. http://dx.doi.org/10.1023/A:1006075007857CrossrefGoogle Scholar

  • [25] Yamagata, M. and Tannock, I.F. The chronic administration of drugs that inhibit the regulation of intracellular pH: invitro and anti-tumour effects. Br. J. Cancer 73 (1996) 1328–1334. Google Scholar

  • [26] Newell, K., Wood, P., Stratford, I. and Tannock, I. Effects of agents which inhibit the regulation of intracellular pH on murine solid tumour. Br. J. Cancer 66 (1992) 311–317. Google Scholar

  • [27] Suzuki, M., Youle, R.J. and Tjandra, N. Structure of bax: co-regulation of dimmer formation and intracellular localization. Cell 103 (2000) 645–654. http://dx.doi.org/10.1016/S0092-8674(00)00167-7CrossrefGoogle Scholar

  • [28] Cartron, P.F., Moreau, C., Oliver, L., Mayat, E., Meflah, K. and Vallette, F.M. Involvement of the N-terminus of bax in its intracellular l ocalization and function. FEBS Lett. 512 (2002) 95–100. http://dx.doi.org/10.1016/S0014-5793(02)02227-5CrossrefGoogle Scholar

  • [29] Gross, A., Jockel, J., Wei, M.C. and Korsmeyer, S.J. Enforced dimerization of bax results its translocation, mitochondrial dysfunction and apoptosis. EMBO J. 17 (1998) 3878–3885. http://dx.doi.org/10.1093/emboj/17.14.3878CrossrefGoogle Scholar

  • [30] Stubbs, M., McSheehy, P.M., Griffiths, J.R. and Bashford, C.L. Causes and consequences of tumor acidity and implications for treatment. Mol. Med. Today 6 (2000) 15–19. http://dx.doi.org/10.1016/S1357-4310(99)01615-9CrossrefGoogle Scholar

About the article

Published Online: 2007-10-29

Published in Print: 2008-03-01


Citation Information: Cellular and Molecular Biology Letters, Volume 13, Issue 1, Pages 119–129, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-007-0042-x.

Export Citation

© 2007 University of Wrocław, Poland. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Tamotsu Kiyoshima, Hisato Yoshida, Hiroko Wada, Kengo Nagata, Hiroaki Fujiwara, Makiko Kihara, Kana Hasegawa, Hirotaka Someya, Hidetaka Sakai, and Hari K. Koul
PLoS ONE, 2013, Volume 8, Number 11, Page e80998
[2]
Wen-juan Wang, Xiao-xing Shi, Yi-wen Liu, Yi-qing He, Ying-zhi Wang, Cui-xia Yang, and Feng Gao
Journal of Cellular Biochemistry, 2013, Volume 114, Number 7, Page 1695
[3]
Konrad Kleszczyński, Stefan Tukaj, Nathalie Kruse, Detlef Zillikens, and Tobias W. Fischer
Journal of Pineal Research, 2013, Volume 54, Number 1, Page 89
[4]
Kenichi Shimada, Timothy R. Crother, Justin Karlin, Jargalsaikhan Dagvadorj, Norika Chiba, Shuang Chen, V. Krishnan Ramanujan, Andrea J. Wolf, Laurent Vergnes, David M. Ojcius, Altan Rentsendorj, Mario Vargas, Candace Guerrero, Yinsheng Wang, Katherine A. Fitzgerald, David M. Underhill, Terrence Town, and Moshe Arditi
Immunity, 2012, Volume 36, Number 3, Page 401
[5]
Mirella Bellocci, Gian Luca Sala, and Simone Prandi
Toxicon, 2011, Volume 57, Number 3, Page 449
[6]
Éva M. Szegő, Attila Csorba, Tamás Janáky, Katalin A. Kékesi, István M. Ábrahám, Gábor M. Mórotz, Botond Penke, Miklós Palkovits, Ünige Murvai, Miklós S.Z. Kellermayer, József Kardos, and Gábor D. Juhász
Neuroendocrinology, 2011, Volume 93, Number 2, Page 90

Comments (0)

Please log in or register to comment.
Log in