Bile acid-induced depolarization of mitochondrial membrane potential preceding cell injury in cultured gastric mucosal cells

J Gastroenterol Hepatol. 1995 Nov-Dec;10(6):621-6. doi: 10.1111/j.1440-1746.1995.tb01360.x.

Abstract

Changes in energy metabolism elicited by sodium taurocholate and their relation to cell viability were determined in gastric mucosal cells. Cultured mucosal cells were labelled with rhodamine-123, a mitochondrial energization-sensitive fluorescence probe, or by propidium iodide, a fluorochrome which labels the nuclei of non-viable cells. The cells were observed under a fluorescence microscope with a laser scanning confocal imaging system. After the addition of sodium taurocholate at concentrations > 5 mol/L, mucosal cells showed a rapid and significant decrease in rhodamine-123 fluorescence. A decrease to 40% of the pretreated values at 30 min was seen with a concentration of sodium taurocholate of 7.5mmol/L. A marked increase in the percentage of propidium iodide-positive cells was noted when the concentration of sodium taurocholate exceeded 5mmol/L. However, the extent of the decrease in rhodamine-123 fluorescence was always greater than the increase in the percentage of propidium iodide-positive cells, suggesting that most of these gastric mucosal cells remained viable. It is therefore suggested that the decrease in rhodamine-123 fluorescence is largely due to the disturbed oxidative phosphorylation of mitochondria. Pretreatment of gastric mucosal cells with low concentrations of ethanol resulted in a significant cytoprotective effect against sodium taurocholate injury with significant prevention of a decrease in rhodamine-123 fluorescence. It is concluded that sodium taurocholate induces a depolarization of the mitochondrial membrane potential preceding cell injury and that the cytoprotective effect of ethanol relates to its attenuation of the uncoupling effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites
  • Cell Count
  • Cell Survival
  • Cells, Cultured
  • Cholagogues and Choleretics / pharmacology*
  • Gastric Mucosa / cytology
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Rabbits
  • Rhodamine 123
  • Rhodamines / pharmacology
  • Taurocholic Acid / pharmacology*

Substances

  • Antimetabolites
  • Cholagogues and Choleretics
  • Rhodamines
  • Rhodamine 123
  • Taurocholic Acid