Mammalian ABC Transporters in Health and Disease
Piet Borst,R.P.J. Oude Elferink +1 more
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TLDR
This work focuses on three topics: ABC transporters transporting drugs (xenotoxins) and drug conjugates, and a rapidly increasing number of ABC Transporters found to play a role in lipid transport.Abstract:
The ATP-binding cassette (ABC) transporters are a family of large proteins in membranes and are able to transport a variety of compounds through membranes against steep concentration gradients at the cost of ATP hydrolysis. The available outline of the human genome contains 48 ABC genes; 16 of these have a known function and 14 are associated with a defined human disease. Major physiological functions of ABC transporters include the transport of lipids, bile salts, toxic compounds, and peptides for antigen presentation or other purposes. We review the functions of mammalian ABC transporters, emphasizing biochemical mechanisms and genetic defects. Our overview illustrates the importance of ABC transporters in human physiology, toxicology, pharmacology, and disease. We focus on three topics: (a) ABC transporters transporting drugs (xenotoxins) and drug conjugates. (b) Mammalian secretory epithelia using ABC transporters to excrete a large number of substances, sometimes against a steep concentration gradient. Several inborn errors in liver metabolism are due to mutations in one of the genes for these pumps; these are discussed. (c) A rapidly increasing number of ABC transporters are found to play a role in lipid transport. Defects in each of these transporters are involved in human inborn or acquired diseases.read more
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References
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Journal ArticleDOI
ABC Transporters: From Microorganisms to Man
TL;DR: This chapter discusses thebuilding blocks of the Transmembrane Complex, and some of the properties of these blocks have changed since the publication of the original manuscript in 1993.
Journal ArticleDOI
Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line
Susan P.C. Cole,Gabu Bhardwaj,James H. Gerlach,J. E. Mackie,Caroline E. Grant,Kurt C. Almquist,Alistair J. Stewart,Ebba U. Kurz,A. M. V. Duncan,Roger G. Deeley +9 more
TL;DR: Reversion to drug sensitivity was associated with loss of gene amplification and a marked decrease in mRNA expression, and the mRNA encodes a member of the ATP-binding cassette transmembrane transporter superfamily.
Journal ArticleDOI
Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo
Sven Hoffmeyer,Oliver Burk,O. von Richter,H. P. Arnold,Jürgen Brockmöller,Andreas Johne,Ingolf Cascorbi,Thomas Gerloff,Ivar Roots,Eichelbaum Michel,Ulrich Brinkmann +10 more
TL;DR: A significant correlation of a polymorphism in exon 26 (C3435T) of MDR-1 with expression levels and function is observed and this polymorphism is expected to affect the absorption and tissue concentrations of numerous other substrates of M DR-1.
Journal ArticleDOI
Identification of a Nuclear Receptor for Bile Acids
Makoto Makishima,Arthur Y. Okamoto,Joyce J. Repa,Hua Tu,R. Marc Learned,Alvin Luk,Mitchell V. Hull,Kevin D. Lustig,David J. Mangelsdorf,Bei Shan +9 more
TL;DR: Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor, which demonstrates a mechanism by which bile acid transcriptionally regulate their biosynthesis and enterohepatic transport.
Journal ArticleDOI
The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype
Sheng Zhou,John D. Schuetz,Kevin D. Bunting,Anne-Marie Colapietro,Janardhan Sampath,John J. Morris,Irina Lagutina,Gerard Grosveld,Mitsujiro Osawa,Hiromitsu Nakauchi,Brian P. Sorrentino +10 more
TL;DR: Results show that expression of the Bcrp1/ABCG2 gene is an important determinant of the SP phenotype, and that it might serve as a marker for stem cells from various sources.