Madin-Darby canine kidney II cells: a pharmacologically validated system for NPC1L1-mediated cholesterol uptake

Molecular Pharmacology
Adam B WeinglassMaria L Garcia

Abstract

Absorption of dietary cholesterol in the proximal region of the intestine is mediated by Niemann-Pick C1-like protein (NPC1L1) and is sensitive to the cholesterol absorption inhibitor ezetimibe (EZE). Although a correlation exists between EZE binding to NPC1L1 in vitro and efficacy in vivo, the precise nature of interaction(s) between NPC1L1, EZE, and cholesterol remain unclear. Here, we analyze the direct relationship between EZE analog binding to NPC1L1 and its influence on cholesterol influx in a novel in vitro system. Using the EZE analog [(3)H]AS, an assay that quantitatively measures the expression of NPC1L1 on the cell surface has been developed. It is noteworthy that whereas two cell lines (CaCo-2 and HepG2) commonly used for studying NPC1L1-dependent processes express almost undetectable levels of NPC1L1 at the cell surface, polarized Madin-Darby canine kidney (MDCKII) cells endogenously express 4 x 10(5) [(3)H]AS sites/cell under basal conditions. Depleting endogenous cholesterol with the HMG CoA reductase inhibitor lovastatin leads to a 2-fold increase in the surface expression of NPC1L1, supporting the contention that MDCKII cells respond to changes in cholesterol homeostasis by up-regulating a pathway for cholester...Continue Reading

References

Jan 1, 1983·Annual Review of Nutrition·S M Grundy
Jul 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·D Louvard
May 27, 1997·Proceedings of the National Academy of Sciences of the United States of America·W Y ChenT M Townes
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·C S ChenR E Pagano
Nov 9, 2002·The American Journal of Cardiology·Claude GagnéUNKNOWN Ezetimibe Study Group
Nov 9, 2002·The American Journal of Cardiology·Carlos A DujovneUNKNOWN Ezetimibe Study Group
Dec 31, 2002·Journal of the American College of Cardiology·Michael H DavidsonEnrico P Veltri
Feb 15, 2003·The American Journal of Cardiology·Boris KerznerUNKNOWN Ezetimibe Study Group
Feb 21, 2004·Science·Scott W AltmannMichael P Graziano
Jul 28, 2004·Biochemistry·Birgit T PriestGregory J Kaczorowski
Dec 18, 2004·Journal of Lipid Research·Jelske N van der VeenFolkert Kuipers
Jan 27, 2005·The Journal of Biological Chemistry·Joanna P DaviesYiannis A Ioannou
Jun 2, 2005·Proceedings of the National Academy of Sciences of the United States of America·Margarita Garcia-CalvoNancy A Thornberry
Jan 13, 2006·The Journal of Biological Chemistry·Liqing YuLawrence L Rudel
Jan 18, 2006·Biochemical and Biophysical Research Communications·Caroline DuvalSophie Lestavel
Jul 11, 2006·Journal of Lipid Research·Alain Théophile SanéEmile Levy
Sep 16, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Murray W HuffRobert A Hegele
Sep 30, 2006·American Journal of Physiology. Gastrointestinal and Liver Physiology·Waddah A AlrefaiRavinder K Gill
Nov 23, 2006·Journal of Lipid Research·Satya N MathurF Jeffrey Field
Dec 1, 2006·The Journal of Pharmacology and Experimental Therapeutics·Yoshihide YamanashiHiroshi Suzuki
Dec 16, 2006·Cell Biology and Toxicology·P Simon-AssmannM Kedinger
May 15, 2007·Current Opinion in Lipidology·Emile LevyMarc-André Lavoie
Jun 20, 2007·European Biophysics Journal : EBJ·Stéphane OrlowskiXavier Collet
Jun 26, 2007·Journal of Atherosclerosis and Thrombosis·Harry R Davis, Enrico P Veltri
Apr 12, 2008·European Journal of Dental Education : Official Journal of the Association for Dental Education in Europe·R OliverD White

❮ Previous
Next ❯

Citations

Aug 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Adam B WeinglassMaria L Garcia
Sep 3, 2010·Annual Review of Physiology·Lin JiaLiqing Yu
Aug 1, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S Kidambi, S B Patel
Mar 24, 2010·FEBS Letters·Jenna L Betters, Liqing Yu
Mar 18, 2016·Cell Death & Disease·A CougnouxF D Porter
Nov 13, 2009·Clinical Pharmacology and Therapeutics·J L Betters, L Yu
Apr 15, 2016·Molecular Biology of the Cell·Tory A Johnson, Suzanne R Pfeffer
Sep 18, 2008·Journal of Lipid Research·Weiqing TangLiqing Yu
Mar 9, 2010·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Bilal AbuasalAmal Kaddoumi
Nov 15, 2020·Biochimica Et Biophysica Acta. Biomembranes·Shunsuke NashimotoYuki Sato

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Proceedings of the National Academy of Sciences of the United States of America
Margarita Garcia-CalvoNancy A Thornberry
© 2021 Meta ULC. All rights reserved