title: Bile acid-induced depolarization of mitochondrial membrane potential preceding cell injury in cultured gastric mucosal cells.
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.
authors.affiliation: Department of Internal Medicine, School of Medicine, Keio University, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Miura
authors.forename: D
authors.initials: D
authors.lastname: Fukumura
authors.forename: H
authors.initials: H
authors.lastname: Shiozaki
authors.forename: M
authors.initials: M
authors.lastname: Suzuki
authors.forename: I
authors.initials: I
authors.lastname: Kurose
authors.forename: M
authors.initials: M
authors.lastname: Suematsu
authors.forename: M
authors.initials: M
authors.lastname: Tsuchiya
authors.forename: H
authors.initials: H
authors.lastname: Ishii
mesh_terms: D000818:Animals; D000963:Antimetabolites; D002452:Cell Count; D002470:Cell Survival; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D020112:Rhodamine 123; D012235:Rhodamines / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology*
chemical_list: D000963:Antimetabolites; D002756:Cholagogues and Choleretics; D012235:Rhodamines; D020112:Rhodamine 123; D013656:Taurocholic Acid