Hydrophilic bile salts enhance differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases: Potential implications for their effects in vivo

Antonio Moschetta, Gerard P. VanBerge-Henegouwen, Piero Portincasa, Willem Renooij, Albert K. Groen, Karel J. Van Erpecum

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Background/Aims: The hepatocyte canalicular membrane outer leaflet contains both phosphatidylcholine (PC) and sphingomyelin (SM). Normally, PC is the exclusive phospholipid in bile. We examined effects of bile salt hydrophobicity on cytotoxicity and on differential SM and PC distribution between detergent-resistant aggregated vesicles (model for detergent-resistant canalicular membrane) and mixed micelles or small unilamellar vesicles (representing lipid phases in bile). Methods: Aggregated vesicles were obtained by ultracentrifugation of cholesterol-supersaturated model systems containing SM, PC and various bile salts, micelles by ultrafiltration and unilamellar vesicles by dialysis of the supernatant. Erythrocyte hemolysis and lactate dehydrogenase release from CaCo-2 cells upon incubation with various micelles were quantified. Results: Preferential SM distribution and lipid solubilization in aggregated vesicles increased in rank order taurodeoxycholate < taurocholate < tauroursodeoxycholate < taurohyodeoxycholate, with reciprocal PC enrichment in micelles and small unilamellar vesicles. Including small amounts of PC within taurohyodeoxycholate micelles increased cytotoxicity with more erythrocyte hemolysis and LDH release from CaCo-2 cells upon incubation, but decreased cytotoxicity in case of tauroursodeoxycholate micelles. Conclusions: Hydrophilic but not hydrophobic bile salts preserve integrity of pathophysiologically relevant phosphatidylcholine plus sphingomyelin-containing bilayers. Enhanced biliary phospholipid secretion during taurohyodeoxycholate but not during tauroursodeoxycholate therapy (Hepatology 25 (1997) 1306) may relate to different interactions of these bile salts with phospholipids.

Original languageEnglish (US)
Pages (from-to)492-499
Number of pages8
JournalJournal of Hepatology
Volume34
Issue number4
DOIs
StatePublished - 2001

Fingerprint

Sphingomyelins
Bile Acids and Salts
Phosphatidylcholines
Micelles
Unilamellar Liposomes
Phospholipids
Caco-2 Cells
Hemolysis
Bile
Detergents
Erythrocytes
Taurodeoxycholic Acid
Lipids
Taurocholic Acid
Membranes
Ultracentrifugation
Ultrafiltration
Gastroenterology
Hydrophobic and Hydrophilic Interactions
L-Lactate Dehydrogenase

Keywords

  • Bile salts
  • Micelles
  • Phosphatidylcholine
  • Sphingomyelin
  • Vesicles

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Hydrophilic bile salts enhance differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases : Potential implications for their effects in vivo. / Moschetta, Antonio; VanBerge-Henegouwen, Gerard P.; Portincasa, Piero; Renooij, Willem; Groen, Albert K.; Van Erpecum, Karel J.

In: Journal of Hepatology, Vol. 34, No. 4, 2001, p. 492-499.

Research output: Contribution to journalArticle

Moschetta, Antonio ; VanBerge-Henegouwen, Gerard P. ; Portincasa, Piero ; Renooij, Willem ; Groen, Albert K. ; Van Erpecum, Karel J. / Hydrophilic bile salts enhance differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases : Potential implications for their effects in vivo. In: Journal of Hepatology. 2001 ; Vol. 34, No. 4. pp. 492-499.
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abstract = "Background/Aims: The hepatocyte canalicular membrane outer leaflet contains both phosphatidylcholine (PC) and sphingomyelin (SM). Normally, PC is the exclusive phospholipid in bile. We examined effects of bile salt hydrophobicity on cytotoxicity and on differential SM and PC distribution between detergent-resistant aggregated vesicles (model for detergent-resistant canalicular membrane) and mixed micelles or small unilamellar vesicles (representing lipid phases in bile). Methods: Aggregated vesicles were obtained by ultracentrifugation of cholesterol-supersaturated model systems containing SM, PC and various bile salts, micelles by ultrafiltration and unilamellar vesicles by dialysis of the supernatant. Erythrocyte hemolysis and lactate dehydrogenase release from CaCo-2 cells upon incubation with various micelles were quantified. Results: Preferential SM distribution and lipid solubilization in aggregated vesicles increased in rank order taurodeoxycholate < taurocholate < tauroursodeoxycholate < taurohyodeoxycholate, with reciprocal PC enrichment in micelles and small unilamellar vesicles. Including small amounts of PC within taurohyodeoxycholate micelles increased cytotoxicity with more erythrocyte hemolysis and LDH release from CaCo-2 cells upon incubation, but decreased cytotoxicity in case of tauroursodeoxycholate micelles. Conclusions: Hydrophilic but not hydrophobic bile salts preserve integrity of pathophysiologically relevant phosphatidylcholine plus sphingomyelin-containing bilayers. Enhanced biliary phospholipid secretion during taurohyodeoxycholate but not during tauroursodeoxycholate therapy (Hepatology 25 (1997) 1306) may relate to different interactions of these bile salts with phospholipids.",
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T2 - Potential implications for their effects in vivo

AU - Moschetta, Antonio

AU - VanBerge-Henegouwen, Gerard P.

AU - Portincasa, Piero

AU - Renooij, Willem

AU - Groen, Albert K.

AU - Van Erpecum, Karel J.

PY - 2001

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N2 - Background/Aims: The hepatocyte canalicular membrane outer leaflet contains both phosphatidylcholine (PC) and sphingomyelin (SM). Normally, PC is the exclusive phospholipid in bile. We examined effects of bile salt hydrophobicity on cytotoxicity and on differential SM and PC distribution between detergent-resistant aggregated vesicles (model for detergent-resistant canalicular membrane) and mixed micelles or small unilamellar vesicles (representing lipid phases in bile). Methods: Aggregated vesicles were obtained by ultracentrifugation of cholesterol-supersaturated model systems containing SM, PC and various bile salts, micelles by ultrafiltration and unilamellar vesicles by dialysis of the supernatant. Erythrocyte hemolysis and lactate dehydrogenase release from CaCo-2 cells upon incubation with various micelles were quantified. Results: Preferential SM distribution and lipid solubilization in aggregated vesicles increased in rank order taurodeoxycholate < taurocholate < tauroursodeoxycholate < taurohyodeoxycholate, with reciprocal PC enrichment in micelles and small unilamellar vesicles. Including small amounts of PC within taurohyodeoxycholate micelles increased cytotoxicity with more erythrocyte hemolysis and LDH release from CaCo-2 cells upon incubation, but decreased cytotoxicity in case of tauroursodeoxycholate micelles. Conclusions: Hydrophilic but not hydrophobic bile salts preserve integrity of pathophysiologically relevant phosphatidylcholine plus sphingomyelin-containing bilayers. Enhanced biliary phospholipid secretion during taurohyodeoxycholate but not during tauroursodeoxycholate therapy (Hepatology 25 (1997) 1306) may relate to different interactions of these bile salts with phospholipids.

AB - Background/Aims: The hepatocyte canalicular membrane outer leaflet contains both phosphatidylcholine (PC) and sphingomyelin (SM). Normally, PC is the exclusive phospholipid in bile. We examined effects of bile salt hydrophobicity on cytotoxicity and on differential SM and PC distribution between detergent-resistant aggregated vesicles (model for detergent-resistant canalicular membrane) and mixed micelles or small unilamellar vesicles (representing lipid phases in bile). Methods: Aggregated vesicles were obtained by ultracentrifugation of cholesterol-supersaturated model systems containing SM, PC and various bile salts, micelles by ultrafiltration and unilamellar vesicles by dialysis of the supernatant. Erythrocyte hemolysis and lactate dehydrogenase release from CaCo-2 cells upon incubation with various micelles were quantified. Results: Preferential SM distribution and lipid solubilization in aggregated vesicles increased in rank order taurodeoxycholate < taurocholate < tauroursodeoxycholate < taurohyodeoxycholate, with reciprocal PC enrichment in micelles and small unilamellar vesicles. Including small amounts of PC within taurohyodeoxycholate micelles increased cytotoxicity with more erythrocyte hemolysis and LDH release from CaCo-2 cells upon incubation, but decreased cytotoxicity in case of tauroursodeoxycholate micelles. Conclusions: Hydrophilic but not hydrophobic bile salts preserve integrity of pathophysiologically relevant phosphatidylcholine plus sphingomyelin-containing bilayers. Enhanced biliary phospholipid secretion during taurohyodeoxycholate but not during tauroursodeoxycholate therapy (Hepatology 25 (1997) 1306) may relate to different interactions of these bile salts with phospholipids.

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KW - Vesicles

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