title: NPC2 is expressed in human and murine liver and secreted into bile: potential implications for body cholesterol homeostasis.
abstract: The liver plays a critical role in the metabolism of lipoprotein cholesterol and in controlling its elimination through the bile. Niemann-Pick type C 2 (NPC2), a cholesterol-binding protein, is key for normal intracellular trafficking of lipoprotein cholesterol, allowing its exit from the endolysosomal pathway into the metabolically active pool of the cell. In addition, NPC2 is a secretory protein from astrocytes and epididymal cells. Although NPC2 mRNA is detected in the liver, plasma and biliary NPC2 protein levels and function have not been reported. This study demonstrates that NPC2 is present in murine and human plasma and bile. In addition, hepatic NPC2 protein expression was dramatically increased in NPC1-deficient mice but not regulated by cholesterol feeding or pharmacological modulation of various nuclear receptors involved in cholesterol and bile acid metabolism. Interestingly, biliary NPC2 levels were 3-fold increased in gallstone-susceptible C57BL6/J versus gallstone-resistant BALB/c mice. Furthermore, NPC2 was exclusively found in the cholesterol pro-nucleating ConA-binding fraction of human bile. In conclusion, NPC2 is secreted from the liver into bile and plasma, where it may have a functional role in cholesterol transport in normal and disease conditions.
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
authors.forename: Andrés
authors.initials: A
authors.lastname: Klein
authors.forename: Ludwig
authors.initials: L
authors.lastname: Amigo
authors.forename: María José
authors.initials: MJ
authors.lastname: Retamal
authors.forename: María Gabriela
authors.initials: MG
authors.lastname: Morales
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Miquel
authors.forename: Attilio
authors.initials: A
authors.lastname: Rigotti
authors.forename: Silvana
authors.initials: S
authors.lastname: Zanlungo
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry*; D002784:Cholesterol / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D008099:Liver / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D033921:Vesicular Transport Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: C497045:Npc2 protein, mouse; D012333:RNA, Messenger; D033921:Vesicular Transport Proteins; D002784:Cholesterol