The Na+/H+ Exchanger Controls Deoxycholic Acid-Induced Apoptosis by a H+-Activated, Na+-Dependent Ionic Shift in Esophageal Cells
2011

The Na+/H+ Exchanger Controls Deoxycholic Acid-Induced Apoptosis in Esophageal Cells

Sample size: 6 publication 10 minutes Evidence: high

Author Information

Author(s): Aaron Goldman, Hwu Chen, Mohammad R. Khan, Heather Roesly, Kimberly A. Hill, Mohammad Shahidullah, Amritlal Mandal, Ruben Claudio Aguilar, Delamere Nicholas A., Katerina Dvorak

Primary Institution: University of Arizona

Hypothesis

The initial acidification induced by deoxycholic acid (DCA) is associated with perturbation of acidic lysosomes.

Conclusion

NHE-mediated Na+ influx is a critical step leading to DCA-induced apoptosis, and cells can evade apoptosis if NHE is inhibited.

Supporting Evidence

  • DCA exposure caused lysosomal membrane perturbation and transient cytoplasmic acidification.
  • Inhibition of NHE with EIPA prevented Na+, K+, and Ca2+ changes and caspase 3/7 activation induced by DCA.
  • Low sodium concentrations inhibited DCA-induced cell death.
  • NHE activation is responsible for Na+ influx in DCA-treated cells.
  • DCA-induced apoptosis was prevented by NHE inhibitors.

Takeaway

When certain cells are exposed to a substance called deoxycholic acid, they can die, but if we block a specific protein that helps sodium enter the cells, they can survive.

Methodology

In vitro studies were conducted using esophageal cell lines treated with deoxycholic acid and various inhibitors to measure ion changes and apoptosis.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0023835

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