Hepatocyte Nuclear Factor 1-alpha

Publication Title: 
Aging Cell

Silent information regulator 2 (Sir2) orthologs are an evolutionarily conserved family of NAD-dependent protein deacetylases that regulate aging and longevity in model organisms. The mammalian Sir2 ortholog Sirt1 regulates metabolic and stress responses through the deacetylation of many transcriptional regulatory factors.

Author(s): 
Grimm, Andrew A.
Brace, Cynthia S.
Wang, Ting
Stormo, Gary D.
Imai, Shin-ichiro
Publication Title: 
The Journal of Biological Chemistry

PCSK9 is a natural inhibitor of LDL receptor (LDLR) that binds the extracellular domain of LDLR and triggers its intracellular degradation. PCSK9 and LDLR are coordinately regulated at the transcriptional level by sterols through their promoter-imbedded sterol response elements (SRE) and co-induced by statins. Identification of regulatory networks modulating PCSK9 transcription is important for developing selective repressors of PCSK9 to improve statin efficacy by prolonging the up-regulation of LDLR.

Author(s): 
Li, Hai
Dong, Bin
Park, Sahng Wook
Lee, Hyun-Sook
Chen, Wei
Liu, Jingwen
Publication Title: 
Journal of Lipid Research

We investigated the role of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the resistance of dyslipidemic hamsters to statin-induced LDL-cholesterol (LDL-C) reduction and the molecular mechanism by which statins modulated PCSK9 gene expression in vivo. We utilized the fructose diet-induced dyslipidemic hamsters as an in vivo model and rosuvastatin to examine its effects on liver PCSK9 and LDL receptor (LDLR) expression and serum lipid levels. We showed that rosuvastatin induced PCSK9 mRNA to a greater extent than LDLR mRNA in the hamster liver.

Author(s): 
Dong, Bin
Wu, Minhao
Li, Hai
Kraemer, Fredric B.
Adeli, Khosrow
Seidah, Nabil G.
Park, Sahng Wook
Liu, Jingwen
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