title: Overexpression of the cholesterol-binding protein MLN64 induces liver damage in the mouse.
abstract: OBJECTIVE
  To examine the in vivo phenotype associated with hepatic metastatic lymph node 64 (MLN64) over-expression.
  
  
  METHODS
  Recombinant-adenovirus-mediated MLN64 gene transfer was used to overexpress MLN64 in the livers of C57BL/6 mice. We measured the effects of MLN64 overexpression on hepatic cholesterol content, bile flow, biliary lipid secretion and apoptosis markers. For in vitro studies cultured CHO cells with transient MLN64 overexpression were utilized and apoptosis by TUNEL assay was measured.
  
  
  RESULTS
  Livers from Ad.MLN64-infected mice exhibited early onset of liver damage and apoptosis. This response correlated with increases in liver cholesterol content and biliary bile acid concentration, and impaired bile flow. We investigated whether liver MLN64 expression could be modulated in a murine model of hepatic injury. We found increased hepatic MLN64 mRNA and protein levels in mice with chenodeoxycholic acid-induced liver damage. In addition, cultured CHO cells with transient MLN64 overexpression showed increased apoptosis.
  
  
  CONCLUSIONS
  In summary, hepatic MLN64 over-expression induced damage and apoptosis in murine livers and altered cholesterol metabolism. Further studies are required to elucidate the relevance of these findings under physiologic and disease conditions.
authors.affiliation: Departamento de Gastroenterologia, Pontificia Universidad Catolica de Chile, Marcoleta 367, Santiago, Chile.
authors.forename: Juan-Enrique
authors.initials: JE
authors.lastname: Tichauer
authors.forename: Maria-Gabriela
authors.initials: MG
authors.lastname: Morales
authors.forename: Ludwig
authors.initials: L
authors.lastname: Amigo
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Galdames
authors.forename: Andres
authors.initials: A
authors.lastname: Klein
authors.forename: Veronica
authors.initials: V
authors.lastname: Quinones
authors.forename: Carla
authors.initials: C
authors.lastname: Ferrada
authors.forename: Alejandra-R
authors.initials: AR
authors.lastname: Alvarez
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Rio
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: D000256:Adenoviridae / Q000235:genetics; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D016466:CHO Cells; D002460:Cell Line; D056486:Chemical and Drug Induced Liver Injury; D002635:Chenodeoxycholic Acid; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: C486529:MLN64 protein, mouse; D010750:Phosphoproteins; D002635:Chenodeoxycholic Acid; D002784:Cholesterol; D000469:Alkaline Phosphatase