title: Inhibition of Ceramide Decreased the Expression of ATP-Binding Cassette Transporter G5/8 mRNA in an Animal Model of Cholesterol Gallstone.
abstract: BACKGROUND
  The increased risk of gallstone has been reported in patients with ATP-binding cassette (ABC) transporter polymorphism. The half-transporters ABCG5 and ABCG8 mediate the efflux of cholesterol in hepatocytes and the intestine. We investigated whether ceramide plays a role in cholesterol efflux through the ABC transporters.
  
  
  METHODS
  Six-week-old C57BL/6J mice were assigned to 3 groups. The normal group (n = 5) was fed a normal chow diet, the cholesterol group (n = 10) was fed a lithogenic diet, and the myriocin group (n = 15) was fed the lithogenic diet and myriocin, a specific inhibitor of serine-palmitoyl transferase. After 6 weeks, the ABCG5 and ABCG8 transporters were analyzed.
  
  
  RESULTS
  The rate of cholesterol gallstone formation in cholesterol group was also higher than that in normal and myriocin groups (0, 70, and 40%, respectively). ABCG5 and ABCG8 mRNA levels were significantly increased in cholesterol group and less increased in myriocin group, relative to that in normal group (p < 0.05).
  
  
  CONCLUSIONS
  The inhibition of ceramide biosynthesis by myriocin suppressed gallstone formation and ABCG5/8 mRNA expression. We expect that ceramide's role as a regulator of the ABCG5/8 transporter might be linked to cholesterol gallstone formation.
authors.affiliation: Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
authors.forename: Hyo Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jae Seon
authors.initials: JS
authors.lastname: Kim
authors.forename: Seikwan
authors.initials: S
authors.lastname: Oh
authors.forename: Hwan-Soo
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5 / Q000235:genetics* / Q000378:metabolism; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8 / Q000235:genetics* / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D002518:Ceramides / Q000037:antagonists & inhibitors* / Q000097:blood; D002784:Cholesterol / Q000378:metabolism*; D004195:Disease Models, Animal; D042882:Gallstones / Q000097:blood / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007082:Ileum / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D002518:Ceramides; D012333:RNA, Messenger; D002784:Cholesterol
keywords: ATP-binding cassette transporter G5; ATP-binding cassette transporter G8; Ceramide