PMID- 17589922 OWN - NLM STAT- MEDLINE DCOM- 20070912 LR - 20190430 IS - 1007-9327 (Print) IS - 2219-2840 (Electronic) IS - 1007-9327 (Linking) VI - 13 IP - 22 DP - 2007 Jun 14 TI - Overexpression of the cholesterol-binding protein MLN64 induces liver damage in the mouse. PG - 3071-9 AB - 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. FAU - Tichauer, Juan-Enrique AU - Tichauer JE AD - Departamento de Gastroenterologia, Pontificia Universidad Catolica de Chile, Marcoleta 367, Santiago, Chile. FAU - Morales, Maria-Gabriela AU - Morales MG FAU - Amigo, Ludwig AU - Amigo L FAU - Galdames, Leopoldo AU - Galdames L FAU - Klein, Andres AU - Klein A FAU - Quinones, Veronica AU - Quinones V FAU - Ferrada, Carla AU - Ferrada C FAU - Alvarez, Alejandra-R AU - Alvarez AR FAU - Rio, Marie-Christine AU - Rio MC FAU - Miquel, Juan-Francisco AU - Miquel JF FAU - Rigotti, Attilio AU - Rigotti A FAU - Zanlungo, Silvana AU - Zanlungo S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - World J Gastroenterol JT - World journal of gastroenterology JID - 100883448 RN - 0 (MLN64 protein, mouse) RN - 0 (Phosphoproteins) RN - 0GEI24LG0J (Chenodeoxycholic Acid) RN - 97C5T2UQ7J (Cholesterol) RN - EC 3.1.3.1 (Alkaline Phosphatase) SB - IM MH - Adenoviridae/genetics MH - Alkaline Phosphatase/blood MH - Animals MH - *Apoptosis MH - CHO Cells MH - Cell Line MH - Chemical and Drug Induced Liver Injury MH - Chenodeoxycholic Acid MH - Cholesterol/metabolism MH - Cricetinae MH - Cricetulus MH - Disease Models, Animal MH - Gene Expression Regulation MH - Humans MH - Liver/metabolism/pathology MH - Liver Diseases/*metabolism/*pathology MH - Mice MH - Mice, Inbred C57BL MH - Phenotype MH - Phosphoproteins/genetics/*metabolism MH - Transfection PMC - PMC4172613 EDAT- 2007/06/26 09:00 MHDA- 2007/09/13 09:00 PMCR- 2007/06/14 CRDT- 2007/06/26 09:00 PHST- 2007/06/26 09:00 [pubmed] PHST- 2007/09/13 09:00 [medline] PHST- 2007/06/26 09:00 [entrez] PHST- 2007/06/14 00:00 [pmc-release] AID - 10.3748/wjg.v13.i22.3071 [doi] PST - ppublish SO - World J Gastroenterol. 2007 Jun 14;13(22):3071-9. doi: 10.3748/wjg.v13.i22.3071.