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Publication : Enhancing effect of taurohyodeoxycholate on ABCB4-mediated phospholipid efflux.

First Author  Ikeda Y Year  2019
Journal  Biochim Biophys Acta Mol Cell Biol Lipids Volume  1864
Issue  10 Pages  1495-1502
PubMed ID  31176036 Mgi Jnum  J:279670
Mgi Id  MGI:6343153 Doi  10.1016/j.bbalip.2019.06.001
Citation  Ikeda Y, et al. (2019) Enhancing effect of taurohyodeoxycholate on ABCB4-mediated phospholipid efflux. Biochim Biophys Acta Mol Cell Biol Lipids 1864(10):1495-1502
abstractText  Hydrophilic bile salts, ursodeoxycholate and hyodeoxycholate, have choleretic effects. ABCB4, a member of the ABC transporter family, is essential for the secretion of phospholipids from hepatocytes into bile. In this study, we assessed the effects of taurine- or glycine-conjugated cholate, ursodeoxycholate and hyodeoxycholate on the ABCB4-mediated phosphatidylcholine (PC) efflux using Abcb4 knockout mice and HEK293 cells stably expressing ABCB4. To evaluate the effects of bile salts on bile formation in Abcb4(+/+) or Abcb4(-/-) mice, the bile was collected during intravenous infusion of saline or bile salts. The biliary PC secretion in Abcb4(+/+) mice was significantly increased by the infusions of all tested bile salts, especially taurohyodeoxycholate. On the other hand, Abcb4(-/-) mice exhibited extremely low secretion of PC into bile, which was not altered by bile salt infusions. We also showed that the PC efflux from ABCB4-expressing HEK293 cells was stimulated by taurohyodeoxycholate much more strongly than the other tested bile salts. However, taurohyodeoxycholate did not restore the activities of ABCB4 mutants. Furthermore, light scattering measurements demonstrated a remarkable ability of taurohyodeoxycholate to form mixed micelles with PC. Therefore, the enhancing effect of taurohyodeoxycholate on the ABCB4-mediated PC efflux may be due to the strong mixed micelle formation ability.
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