The role of phosphatidylethanolamine methyltransferase in a mouse model of intrahepatic cholestasis

Zhaoyu Li, Luis B. Agellon, Dennis E. Vance

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Intrahepatic cholestasis eventually leads to liver failure. We report here a condition that decreases liver damage in intrahepatic cholestasis based on a mouse model that lacks multiple drug resistant protein 2 (ABCB4). We found that lack of phosphatidylethanolamine N-methyltransferase (PEMT) decreased liver damage in Abcb4-/- mice caused by exposure of the liver to excess bile acids. The protective effect was not related to hepatic ratio of phosphatidylcholine to phosphatidylethanolamine or the level of cholesterol. The decreased concentration of bile acids in liver was related to impaired re-absorption of bile acids in intestine and increased disposal of bile acids in feces in Abcb4-/-/Pemt-/- mice as compared to Abcb4 -/- mice. PEMT deficiency affected intestinal Na+ absorption resulting in an impaired Na+ concentration gradient along the length of the small intestine and abnormal absorption of bile acids mediated by apical sodium-dependent bile acid transporter (ASBT). The findings of this study suggest that inhibition of PEMT and/or reduction of intestinal sodium concentration may be helpful in attenuating liver damage and prolonging hepatic function in intrahepatic cholestasis.

Original languageEnglish (US)
Pages (from-to)278-283
Number of pages6
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1811
Issue number4
DOIs
StatePublished - Apr 1 2011

Keywords

  • ABCB4
  • Cholestasis
  • Mdr2
  • PFIC3
  • Sodium

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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