Welcome! Click here to login or here to register.
DNA damage
Draw a picture

Bujnicki Lab Homepage

"Expression of apolipoprotein C-IV is regulated by Ku antigen/peroxisome proliferator-activated receptor gamma complex and correlates with liver steatosis."

Kim E, Li K, Lieu C, Tong S, Kawai S, Fukutomi T, Zhou Y, Wands J, Li J

Published Nov. 1, 2008 in J Hepatol volume 49 .

Pubmed ID: 18809223

BACKGROUND/AIMS: We previously reported that hepatitis C virus (HCV) core protein up regulated transcription of apolipoprotein C-IV (ApoC-IV, 10.7-fold increase), a member of the apolipoprotein family implicated in liver steatosis. Here, we identified host transcription factors regulating the ApoC-IV gene expression. METHODS: Transcriptional regulators were identified by DNA affinity purification and steatosis was detected by oil red O staining and triglyceride assay. RESULTS: We defined a 163-bp ApoC-IV promoter as a core protein responsive element, and identified Ku antigen complex (Ku70 and Ku80) as well as nuclear receptors PPARgamma/RXRalpha as key regulators of ApoC-IV gene expression. Both Ku70 overexpression and PPARgamma agonist significantly increased ApoC-IV promoter activity; conversely, Ku70 silencing or mutation of PPARgamma binding site diminished the ApoC-IV promoter activity. Interestingly, transient transfection of ApoC-IV cDNA into a human hepatoma cell line was able to trigger moderate lipid accumulation. In agreement with this in vitro study, ApoC-IV transcript level was increased in HCV infected livers which correlated with triglyceride accumulation. CONCLUSIONS: ApoC-IV overexpression may perturb lipid metabolism leading to lipid accumulation. HCV core protein may modulate ApoC-IV expression through Ku antigen and PPARgamma/RXRalpha complex.

This publication refers to following REPAIRtoire entries:


Last modification of this entry: Oct. 6, 2010

Add your own comment!

There is no comment yet.
Welcome stranger! Click here to login or here to register.
Valid HTML 4.01! This site is Emacs powered. Made with Django.