Basic Research
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jun 14, 2007; 13(22): 3071-3079
Published online Jun 14, 2007. doi: 10.3748/wjg.v13.i22.3071
Overexpression of the cholesterol-binding protein MLN64 induces liver damage in the mouse
Juan Enrique Tichauer, María Gabriela Morales, Ludwig Amigo, Leopoldo Galdames, Andrés Klein, Verónica Quiñones, Carla Ferrada, Alejandra Alvarez R, Marie-Christine Rio, Juan Francisco Miquel, Attilio Rigotti, Silvana Zanlungo
Juan Enrique Tichauer, María Gabriela Morales, Ludwig Amigo, Leopoldo Galdames, Andrés Klein, Verónica Quiñones, Carla Ferrada, Juan Francisco Miquel, Attilio Rigotti, Silvana Zanlungo, Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile
Alejandra Alvarez R, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Uni-versidad Católica, Santiago, Chile
Marie-Christine Rio, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U596, 67404 Illkirch, France
Author contributions: All authors contributed equally to the work.
Supported by Fondo Nacional de Desarrollo Científico y Tecnológico, FONDECYT grant No. 1030415 to S.Z. and No. 1030416 to A.R.
Correspondence to: Dr. Silvana Zanlungo, Pontificia Uni-versidad Católica de Chile, Departamento de Gastroenterología, Marcoleta 367, Santiago, Chile. silvana@med.puc.cl
Telephone: +56-2-6863820  Fax: +56-2-6397780
Received: February 27, 2007
Revised: March 20, 2007
Accepted: March 28, 2007
Published online: June 14, 2007
Abstract

AIM: 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.

CONCLUSION: 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.

Keywords: Metastatic lymph node 64; Apoptosis; Cholesterol; Liver; StarD3