TY - JOUR
T1 - Effects of bile salts on cholestan-3β,5α,6β-triol-induced apoptosis in dog gallbladder epithelial cells
AU - Yoshida, Tadashi
AU - Klinkspoor, J. Henriëtte
AU - Kuver, Rahul
AU - Poot, Martin
AU - Rabinovitch, Peter S.
AU - Wrenn, Steven P.
AU - Kaler, Eric W.
AU - Lee, Sum P.
N1 - Funding Information:
This work was supported by the Medical Research Service of the Department of Veterans Affairs.
PY - 2001/2/26
Y1 - 2001/2/26
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Bile salt
KW - Biliary tract
KW - Gall bladder
KW - Oxysterol
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U2 - 10.1016/S1388-1981(00)00183-9
DO - 10.1016/S1388-1981(00)00183-9
M3 - Article
C2 - 11239822
AN - SCOPUS:0035952337
SN - 1388-1981
VL - 1530
SP - 199
EP - 208
JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
IS - 2-3
ER -