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

Authors:
  • XLXiao-Bing Liu
    Xiao-Bing Liu
  • RMRejei Masago
    Rejei Masago
  • NVNorma Vela-Roch
    Norma Vela-Roch
  • FJFabio Jimenez
    Fabio Jimenez
  • CLChe-Ming A Lau
    Che-Ming A Lau
  • VFVictoria C Frohlich
    Victoria C Frohlich
  • NTNorman Talal
    Norman Talal
  • HDHoward Dang
    Howard Dang
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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 Ca(2+) and Ca(2+) influx. Carbachol-mediated release of Ca(2+) from intracellular stores was significantly higher in Bax transfectants compared to control transfectants (empty vector). Ca(2+) influx was also increased in Bax transfectants. Bax had no affect on the storage operated channels. However, the concentration of Ca(2+) 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 Ca(2+) mobilization and storage capacity in the mitochondria to control levels. This study shows that sub-apoptotic levels of Bax can reduce Ca(2+) content in intracellular stores and Ca(2+) homeostasis. Bax may mediate these effects by reducing the levels of antioxidants resulting in mild oxidative stress.

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