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

Sonomi Aiba-Masago, Xiao Bing Liu, Rejei Masago, Norma Vela-Roch, Fabio Jimenez, Che Ming A. Lau, Victoria C. Frohlich, Norman Talal, Howard Dang

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2762-2767
Number of pages6
JournalOncogene
Volume21
Issue number17
DOIs
Publication statusPublished - Apr 18 2002

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Keywords

  • Bcl-2 family
  • Calcium
  • Glutathione
  • Muscarinic receptor
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Aiba-Masago, S., Liu, X. B., Masago, R., Vela-Roch, N., Jimenez, F., Lau, C. M. A., ... Dang, H. (2002). Bax gene expression alters Ca2+ signal transduction without affecting apoptosis in an epithelial cell line. Oncogene, 21(17), 2762-2767. https://doi.org/10.1038/sj.onc.1205369