Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Report
  • Published:

Bax gene expression alters Ca2+ signal transduction without affecting apoptosis in an epithelial cell line

Oncogene volume 21, pages 2762–2767 (2002)Cite this article

Abstract

Bax is an oncogene that has proapoptotic properties but not all cells that express Bax undergo apoptosis. Bax may have a function unrelated to apoptosis. To elucidate the role of Bax in cell signaling, an epithelial cell line called SMG-C6 was transfected with the human bax gene. Stable transfectants were studied for their response to carbachol, a muscarinic receptor agonist, by measuring the increase in intracellular free Ca2+ and Ca2+ influx. Carbachol-mediated release of Ca2+ from intracellular stores was significantly higher in Bax transfectants compared to control transfectants (empty vector). Ca2+ influx was also increased in Bax transfectants. Bax had no affect on the storage operated channels. However, the concentration of Ca2+ in the intracellular stores (i.e., mitochondria and granules) was 40–50% lower in the Bax transfectants. There was no significant difference in thapsigargin-mediated apoptosis in Bax transfectants compared to wild-type and control transfectants. Measurement of glutathione was reduced in the Bax transfectant. Restoration of glutathione levels with glutathione monoethyl ester partially normalized Ca2+ mobilization and storage capacity in the mitochondria to control levels. This study shows that sub-apoptotic levels of Bax can reduce Ca2+ content in intracellular stores and Ca2+ homeostasis. Bax may mediate these effects by reducing the levels of antioxidants resulting in mild oxidative stress.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Azhar G, Liu L, Zhang X, Wei JY . 1999 Mech. Ageing Dev. 112: 5–25

  • Bargou RC, Wagener C, Bommert K, Mapara MY, Daniel PT, Arnold W, Dietel M, Guski H, Feller A, Royer HD, Dorken B . 1996 J. Clin. Invest. 97: 2651–2659

  • Boise LH, Gonzalez-Garcia M, Postema CE, Ding L, Lindsten T, Turka LA, Mao X, Nunez G, Thompson CB . 1993 Cell 74: 597–608

  • Bojes HK, Datta K, Xu J, Chin A, Simonian P, Nunez G, Kehrer JP . 1997 Biochem. J. 325: 315–319

  • Brady HJ, Gil-Gomez G, Kirberg J, Berns AJ . 1996 EMBO J. 15: 6991–7001

  • Buttke TM, Sandstrom PA . 1995 Free Radic. Res. 22: 389–397

  • Desagher S, Osen-Sand A, Nichols A, Eskes R, Montessuit S, Lauper S, Maundrell K, Antonsson B, Martinou JC . 1999 J. Cell. Biol. 144: 891–901

  • Foyouzi-Youssefi R, Arnaudeau S, Borner C, Kelley WL, Tschopp J, Lew DP, Demaurex N, Krause KH . 2000 Proc. Natl. Acad. Sci. USA 97: 5723–5728

  • Ghibelli L, Coppola S, Fanelli C, Rotilio G, Civitareale P, Scovassi AI, Ciriolo MR . 1999 FASEB J. 13: 2031–2036

  • Ghibelli L, Coppola S, Rotilio G, Lafavia E, Maresca V, Ciriolo MR . 1995 Biochem. Biophys. Res. Commun. 216: 313–320

  • Gross A, McDonnell JM, Korsmeyer SJ . 1999 Genes Dev. 13: 1899–1911

  • Grynkiewicz G, Poenie M, Tsien RY . 1985 J. Biol. Chem. 260: 3440–3450

  • Hehner SP, Breitkreutz R, Shubinsky G, Unsoeld H, Schulze-Osthoff K, Schmitz ML, Dröge W . 2000 J. Immunol. 165: 4319–4328

  • Ichimiya M, Chang SH, Liu H, Berezesky IK, Trump BF, Amstad PA . 1998 Am. J. Pathol. 275: C832–C839

  • Kampranis SC, Damianova R, Atallah M, Toby G, Kondi G, Tsichlis PN, Makris AM . 2000 J. Biol. Chem. 275: 29207–29216

  • Kong L, Ogawa N, McGuff HS, Nakabayashi T, Sakata KM, Masago R, Vela-Roch N, Talal N, Dang H . 1998 Clin. Immunol. Immunopathol. 88: 133–141

  • Krajewski S, Krajewska M, Shabaik A, Miyashita T, Wang HG, Reed JC . 1994 Am. J. Pathol. 145: 1323–1336

  • Kuo TH, Kim HR, Zhu L, Yu Y, Lin HM, Tsang W . 1998 Oncogene 17: 1903–1910

  • Masago R, Aiba-Masago S, Talal N, Zuluaga FJ, Al-Hashimi I, Moody M, Lau CA, Peck AB, Brayer J, Humphreys-Beher MG, Dang H . 2001 Arthritis Rheum. 44: 693–702

  • McConkey D, Orrenius S . 1996 J. Leukoc. Biol. 59: 775–783

  • Metivier D, Dallaporta B, Zamzami N, Larochette N, Susin SA, Marzo I, Kroemer G . 1998 Immunol. Lett. 61: 157–163

  • Murphy AN, Bredesen DE, Cortopassi G, Wang E, Fiskum G . 1996 Proc. Natl. Acad. Sci. USA 93: 9893–9898

  • Naarala J, Tervo P, Loikkanen J, Savolainen K . 1997 Life Sci. 60: 1905–1914

  • Nicoletti I, Migliorati G, Pagliacci MC, Grigani F, Riccardi C . 1991 J. Immunol. Meth. 139: 271–279

  • Nutt LK, Pataer A, Pahler J, Fang B, Roth J, McConkey DJ, Swisher SG . 2002 J. Biol. Chem. in press 10.1074/jbc.m106817200

  • Ohlsson M, Skarstein K, Bolstad AI, Johannessen AC, Jonsson R . 2001 Lab. Invest. 81: 95–105

  • Olive M, Ferrer I . 1999 J. Neurol. Sci. 164: 76–81

  • Penault-Llorca F, Bouabdallah R, Devilard E, Charton-Bain MC, Hassoun J, Birg F, Xerri L . 1998 Pathol. Res. Pract. 194: 457–464

  • Pinton P, Ferrari D, Magalhaes P, Schulze-Osthoff K, Di Virgilio F, Pozzan T, Rizzuto R . 2000 J. Cell. Biol. 148: 857–862

  • Polihronis M, Tapinos NI, Theocharis SE, Economou A, Kittas C, Moutsopoulos HM . 1998 Clin. Exp. Immunol. 114: 485–490

  • Quissell DO, Barzen KA, Gruenert DC, Redman RS, Camden JM, Turner JT . 1997 In Vitro Cell. Dev. Biol. Anim. 33: 164–173

  • Staal FJ, Anderson MT, Staal GE, Herzenberg LA, Gitler C . 1994 Proc. Natl. Acad. Sci. USA 91: 3619–3622

  • Wang H, Joseph JA . 2000 Free Radic. Biol. Med. 28: 1222–1231

  • Wei H, Wei W, Bredesen DE, Perry DC . 1998 J. Neurochem. 70: 2305–2314

  • Zhang GH, Helmke RJ, Martinez JR . 1997 Proc. Soc. Exp. Biol. Med. 216: 117–124

  • Zhou YP, Pena JC, Roe MW, Mittal A, Levisetti M, Baldwin AC, Pugh W, Ostrega D, Ahmed N, Bindokas VP, Philipson LH, Hanahan D, Thompson CB, Polonsky KS . 2000 Am. J. Physiol.-Endocrinol. Metab. 278: E340–E351

Download references

Acknowledgements

The authors thank Charles Thomas for flow cytometry analysis. This work was supported by Public Health Service grant DE12203 from National Institutes of Health (NIDCR).

Author information

Author notes

  1. Sonomi Aiba-Masago and Xiao-bing Liu: S Aiba-Masago and X-b Liu have made equal contributions to this work

Authors and Affiliations

  1. Department of Community Dentistry, University of Texas Health Science Center, San Antonio, 78229-3900, Texas, TX, USA

    Sonomi Aiba-Masago, Xiao-bing Liu, Rejei Masago, Norma Vela-Roch, Fabio Jimenez & Howard Dang

  2. Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, Texas, 78229-3900, TX, USA

    Victoria C Frohlich

  3. Harcourt Brace Educational Measurement, San Antonio, 78204-2498, Texas, TX, USA

    Che-Ming A Lau

  4. Columbia University College of Physicians and Surgeons, New York, 10019, NY, USA

    Norman Talal

Authors
  1. Sonomi Aiba-Masago
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiao-bing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rejei Masago
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Norma Vela-Roch
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Fabio Jimenez
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Che-Ming A Lau
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Victoria C Frohlich
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Norman Talal
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Howard Dang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Howard Dang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aiba-Masago, S., Liu, Xb., Masago, R. et al. Bax gene expression alters Ca2+ signal transduction without affecting apoptosis in an epithelial cell line. Oncogene 21, 2762–2767 (2002). https://doi.org/10.1038/sj.onc.1205369

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205369

Keywords

Search

Advanced search

Quick links