Effects of bile salts on cholestan-3β,5α,6β-triol-induced apoptosis in dog gallbladder epithelial cells

Tadashi Yoshida, J. Henriëtte Klinkspoor, Rahul Kuver, Martin Poot, Peter S. Rabinovitch, Steven P. Wrenn, Eric W. Kaler, Sum P. Lee

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Oxysterols are cytotoxic agents. The gallbladder epithelium is exposed to high concentrations of oxysterols, and so elucidating the mechanisms of cytotoxicity in this organ may enhance our understanding of the pathogenesis of biliary tract disorders. We investigated the cytotoxic effects of the oxysterol cholestan-3β,5α,6β-triol (TriolC) on dog gallbladder epithelial cells. Apoptosis was the major form of cytotoxicity, as determined by analysis of nuclear morphologic changes and by multiparameter flow cytometry. Hydrophobic bile salts are known to have cytotoxic effects, whereas hydrophilic bile salts have cytoprotective effects. We therefore examined whether the hydrophobic bile acid taurodeoxycholic acid (TDC) and the hydrophilic bile acid tauroursodeoxycholic acid (TUDC) had modifying effects on oxysterol-induced cytotoxicity. TriolC caused an increase in the number of apoptotic cells from 14 ± 11% (control) to 48 ± 12% of total cells (P < 0.01). After combining TriolC with TDC, cell apoptosis increased to 63 ± 16% (P < 0.05), whereas after addition of TUDC, the number of apoptotic cells decreased to 31 ± 12% (P < 0.05) of total cells. In summary, oxysterols such as TriolC induce apoptosis. Hydrophobic bile salts enhance TriolC-induced apoptosis, whereas hydrophilic bile salts diminish TriolC-induced apoptosis. These results suggest that interactions between oxysterols and bile salts play a role in the pathophysiology of biliary tract disorders.

Original languageEnglish (US)
Pages (from-to)199-208
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1530
Issue number2-3
DOIs
StatePublished - Feb 26 2001

Keywords

  • Apoptosis
  • Bile salt
  • Biliary tract
  • Gall bladder
  • Oxysterol

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