Oxysterols from human bile induce apoptosis of canine gallbladder epithelial cells in monolayer culture

American Journal of Physiology. Gastrointestinal and Liver Physiology
Dong Wan SeoR Kuver

Abstract

Oxysterols have been detected in various mammalian organs and blood. Biliary epithelium is exposed to high concentrations of cholesterol, and we have identified three keto-oxysterols (cholest-4-en-3-one, cholesta-4,6-dien-3-one, cholesta-3,5-dien-7-one) in human bile and gallstones. Because the effects of oxysterols on biliary physiology are not well defined, we investigated their biological effects on dog gallbladder epithelial cells. Enriched medium (culture medium containing taurocholate and lecithin and cholesterol +/- various oxysterols) was applied to confluent monolayers of dog gallbladder epithelial cells in culture. Cytotoxicity and apoptosis were studied by morphological analysis and flow cytometry. Oxysterols in the mitochondrial fraction were identified by gas chromatography/mass spectrometry, whereas release of cytochrome c from mitochondria was assayed by spectrophotometry and Western blot analysis. Compared with cells treated with culture medium or with enriched medium containing cholesterol, oxysterol-treated cells showed significantly increased apoptosis (P < 0.05). Exogenously applied oxysterols were recovered from the mitochondrial fraction. Cytochrome c release from mitochondria was increased significantly b...Continue Reading

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Citations

Mar 21, 2006·Biochemical and Biophysical Research Communications·W Geoffrey HaighSum P Lee
Aug 21, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Apinya JusakulPuangrat Yongvanit
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Mar 17, 2020·Current Medicinal Chemistry·Afshin SamadiMassimiliano Peana

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