HNF4α is a Crucial Modulator of the Cholesterol-Dependent Regulation of NPC1L1

Yuki Iwayanagi; Tappei Takada; Hiroshi Suzuki
May 2008
Pharmaceutical Research;May2008, Vol. 25 Issue 5, p1134
Academic Journal
Abstract Purpose  Niemann-Pick C1-like 1 (NPC1L1) has been identified as a target of ezetimibe and found to be responsible for intestinal cholesterol absorption. Although, it was recently demonstrated that sterol responsive element binding protein 2 (SREBP2) is responsible for the cholesterol-dependent down-regulation of NPC1L1, the molecular mechanism of NPC1L1 expression is not fully understood. In the present study, we examined the involvement of hepatocyte nuclear factor 4α (HNF4α), a key modulator of lipid metabolism, in the transcriptional regulation of human NPC1L1 gene. Methods  Reporter gene assays and EMSAs were performed using human NPC1L1 promoter constructs and the effect of siHNF4α was examined. Results  Transfection of SREBP2 induced the transcriptional activities of NPC1L1 and additional transfection of HNF4α results in a marked stimulation of the activities. Studies with deletion mutants indicated that important elements are located within 264 nt upstream in the human NPC1L1 promoter. In addition, studies with mutations in putative binding sites of HNF4α indicated the existence of binding sites in −209 to −197 and −52 to −40. Moreover, HNF4α knockdown resulted in the reduced expression and regulation by cholesterol. Conclusions  It is concluded that HNF4α plays a crucial role in the expression and regulation of human NPC1L1 gene.


Related Articles

  • FORMULATION AND IN VITRO EVALUTION OF DIACEREIN LOADED NIOSOMES. ZAKI, RANDA M.; ALI, ADEL A.; MENSHAWE, SHAHIRA F. EL; BARY, AHMED ABDEL // International Journal of Pharmacy & Pharmaceutical Sciences;2014 Supplement 2, p515 

    Objective: Diacerein is poorly water soluble non steroidal anti-inflammatory drug belongs to BCS class II with low oral bioavailability. This research aimed towards formulation and evaluation of successful diacerein loaded niosomes in order to improve dissolution and hence its oral...

  • Fat Loss Depends on Energy Deficit Only, Independently of the Method for Weight Loss. Strasser, B.; Spreitzer, A.; Haber, P. // Annals of Nutrition & Metabolism;Sep2007, Vol. 51 Issue 5, p428 

    Background: This study was designed to compare the effects of 2 different but isocaloric fat reduction programs with the same amount of energy deficit – diet alone or diet combined with aerobic training – on body composition, lipid profile and cardiorespiratory fitness in non- or...

  • Hypocholesterolemic Effects of the LDL Receptor Gene Transcriptional Upregulator CP-230821. Shimokawa, Teruhiko; Goto, Shoichiro; Ida, Motoko; Goto, Masahide; Nishijima, Satomi; Kodama, Tatsuhiko // Journal of Biochemistry;1998, Vol. 123 Issue 4, p596 

    CP-230821 is a novel, potent LDL receptor gene transcriptional upregulator which decreases total plasma cholesterol level. Interestingly, this plasma LDL decrease does not alter hepatic lipid contents. A series of experiments was undertaken to study the molecular biology of this phenomenon....

  • Synthesis and molecular docking studies of certain chalcones of benzimidzole. Chandran, Meena // Journal of Pharmacy Research;2012, Vol. 5 Issue 1, p324 

    Molecular docking is routinely used for understanding drug-receptor interaction in modern drug design. In the present work involved the synthesis of three different chalcones of benzimidazole by three steps. Initially by using a o-phenylenediamine and lactic acid as the starting materials for...

  • Efficacy and safety of replacing lopinavir with atazanavir in HIV-infected patients with undetectable plasma viraemia: final results of the SLOAT trial. Vincent Soriano; Pilar García-Gasco; Eugenia Vispo; Andrés Ruiz-Sancho; Francisco Blanco; Luz Martín-Carbonero; Sonia Rodríguez-Novoa; Judit Morello; Carmen de Mendoza; Pablo Rivas; Pablo Barreiro; Juan González-Lahoz // Journal of Antimicrobial Chemotherapy (JAC);Jan2008, Vol. 61 Issue 1, p200 

    : Background Atazanavir seems to be a protease inhibitor (PI) with a more favourable metabolic profile. Information regarding the potential benefit of replacing lopinavir/ritonavir by atazanavir in HIV-infected patients with prolonged viral suppression is scarce. If proved, this strategy could...

  • Lower HDL-cholesterol among healthy middle-aged Japanese-Brazilians in São Paulo compared to Natives and Japanese-Brazilians in Japan. Andiara Schwingel; Wojtek Chodzko-Zajko; Ryosuke Shigematsu; Christopher Erb; Simone Souza; Tomoaki Matsuo; Suely Marie // European Journal of Epidemiology;Jan2007, Vol. 22 Issue 1, p33 

    Abstract??Blood lipid levels are determined by a combination of genetic and environmental factors. Higher than average values of high-density lipoprotein cholesterol (HDL-cholesterol) have been observed in people of Japanese ethnicity. The aim of this study was to investigate whether Japanese...

  • Mitochondrial membrane cholesterol, the voltage dependent anion channel (VDAC), and the Warburg effect. Andrew Campbell; Samuel Chan // Journal of Bioenergetics & Biomembranes;Jun2008, Vol. 40 Issue 3, p193 

    Abstract  Normal cells of aerobic organisms synthesize the energy they require in the form of ATP via the process of oxidative phosphorylation. This complex system resides in the mitochondria of cells and utilizes oxygen to produce a majority of cellular ATP. However, in most tumors,...

  • Do we need lipid clinics? Shifting the balance between secondary and primary care. Stuart, W; Smellie, A // Annals of Clinical Biochemistry;Nov2005, Vol. 42 Issue 6, p463 

    Background: Increasing activity in cholesterol lowering is placing increasing demands on lipid clinics to be able to cope with the increase in demand. A combination of interventions has been used to improve laboratory testing, focus interpretative results and provide educational and advisory...

  • False negative results in the Roche assay for HDL-cholesterol. Bakker, Andries J; Zijlstra, Appie; Leemhuis, Marten P // Annals of Clinical Biochemistry;Sep2003, Vol. 40 Issue 5, p572 

    Measurement of HDL-cholesterol is important in the risk evaluation of cardiovascular disease. Recently, we encountered a 61-year-old man with a negative result for HDL-cholesterol using the Roche assay. Further analysis revealed that this patient had a monoclonal Ig type IgMκ, with an...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics