Download or read book Functional Analysis of ATP Binding Cassette ABC Transporters in Caenorhabditis Elegans written by Zhongying Zhao and published by . This book was released on 2005 with total page 374 pages. Available in PDF, EPUB and Kindle. Book excerpt: This thesis deals with functional analysis of ABC transporter genes in Caenorhabditis elegans. ABC transporters constitute one of the largest gene families in C. elegans. Sixty ABC genes have been identified and classified into eight different subfamilies. Fifty-seven orthologous pairs can be found between C. elegans and C. briggsae. As an initial step toward understanding the functions of the ABC genes, I generated transgenic animals containing prornoter::GFP/DsRed fusion constructs for the whole family in order to address when and where these genes are turned on in vivo. I observed frequent expression of ABC genes in intestine, pharynx and excretory cell, especially for those in subfamilies B and C. Sixteen of the 60 ABC genes are tandemly duplicated genes, forming two 4-gene and four 2-gene clusters. Interestingly, the majority of the promoters from the same clusters drive temporally andfor spatially differential expressions, suggesting active function of these duplicated genes in different tissues or stages rather than their being inactivated, as is typical for duplicated genes. Currently 18 single ABC gene mutants have been created. All of them are wild type under normal laboratory conditions. I used one of the ABC genes, pgp-12, an excretory cell-expressing gene, to characterize its transcriptional regulation. A 10 base pair (bp) cis-element, Ex-1 and its binding protein C26C6.5a, were isolated. C26C6.5a is also expressed in the excretory cell and binds Ex-l in vitro. RNAi analysis revealed that the C26C6.5a protein functions as a trans-activator for excretory cell specific expression. The only member of subfamily E is the ABCE gene that has been annotated as an RNase L inhibitor. This annotation is unlikely to be correct because of the lack of the inhibitor gene in C. elegans. Functional analysis of the gene reveals that it is essential for life, possibly involved in transcription and translation, and may function as a nucleocytoplasrnic transporter. RNAi data implies that the protein functions in both germline and vulvae.
Download or read book The Human ATP binding Cassette ABC Transporter Superfamily written by Michael Carlton Dean and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Plant ABC Transporters written by Markus Geisler and published by Springer. This book was released on 2014-09-06 with total page 333 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is devoted to the fascinating superfamily of plant ATP-binding cassette (ABC) transporters and their variety of transported substrates. It highlights their exciting biological functions, covering aspects ranging from cellular detoxification, through development, to symbiosis and defense. Moreover, it also includes a number of chapters that center on ABC transporters from non-Arabidopsis species. ABC proteins are ubiquitous, membrane-intrinsic transporters that catalyze the primary (ATP-dependent) movement of their substrates through biological membranes. Initially identified as an essential aspect of a vacuolar detoxification process, genetic work in the last decade has revealed an unexpectedly diverse variety of ABC transporter substrates, which include not only xenobiotic conjugates, but also heavy metals, lipids, terpenoids, lignols, alkaloids and organic acids. The discovery that members of the ABCB and ABCG family are involved in the movement of phytohormones has further sparked their exploration and provided a new understanding of the whole family. Accordingly, the trafficking, regulation and structure-function of ABCB-type auxin transporters are especially emphasized in this book.
Download or read book The ABC Transporters of Human Physiology and Disease written by Kenneth J. Linton and published by World Scientific. This book was released on 2011 with total page 478 pages. Available in PDF, EPUB and Kindle. Book excerpt: ATP Binding Cassette (ABC) transporters are a family of integral membrane proteins present in all cells of all species of archaea, eubacteria and eukaryota. The vast majority of these proteins control the transport across cellular membranes of molecules ranging from small ions to drugs, lipids and proteins. The human genome encodes 48 ABC transporter genes and mutations in most have been linked to disease. This book OCo that brings together state-of-the-art knowledge on ABC proteins in one volume OCo will provide students, professors and medical professionals with a background to the human ABC transporters that are known to be relevant to disease. Each of the 14 chapters is written by a leading researcher in the field. The genetics, structure and function of the proteins, and the future direction of research including the implications for human health are discussed in depth.
Download or read book ABC Transporters in Human Disease written by Karobi Moitra and published by Morgan & Claypool Publishers. This book was released on 2012-04-20 with total page 87 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ATP-binding cassette (ABC) transporter genes are ubiquitous in the genomes of all vertebrates so far studied. The human ABC transporter superfamily contains 48 genes, subdivided into 7 subfamilies ranging from A to G (based on sequence homology of their nucleotide binding domains). The ABC proteins encoded by these genes are ATP-driven transmembrane pumps, some of which possess the capacity to efflux harmful toxic substances and therefore play a key role in xenobiotic defense. ABC proteins have been evolutionarily conserved from bacteria to humans and multiple gene duplication and deletion events in the ABC genes indicate that the process of gene evolution is still ongoing. Polymorphisms and variations in these genes are linked to variations in expression, function, drug disposition, and drug response. Single nucleotide polymorphisms (SNPs) in these genes could be markers of individual risk for adverse drug reactions or susceptibility to complex diseases. The pharmacogenetics of this unique family of transporters is still under study; however, in the context of human health, it is a well-known fact that variations in these transporters are the underlying cause for several human diseases including cystic fibrosis, Pseudoxanthoma elasticum (PXE), and X-linked adenoleukodystrophy (X-ALD). Table of Contents: Introduction to the Human ATP-Binding Cassette (ABC) Transporter Superfamily / Evolution of ABC Transporters / Overview of ABC Transporters in Human Disease / The Cystic Fibrosis Transmembrane Conductance Regulator-ABCC7 / PXE / X-linked Adrenoleukodystrophy / ABC Proteins: A Global Perspective / References / Titles of Related Interest
Download or read book Structure and Function Analysis of the Mammalian ATP binding Cassette Transporters ABCB1 and ABCB4 written by Michael Nicolaou and published by . This book was released on 2012 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Human ATP binding Cassette ABC Transporter Superfamily written by Michael Carlton Dean and published by . This book was released on 2002 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book ABC Proteins written by I Barry Holland and published by Elsevier. This book was released on 2003-01-07 with total page 672 pages. Available in PDF, EPUB and Kindle. Book excerpt: ABC Proteins is an in-depth, up-to-date analysis of all that is known about the subject to date. It discusses and compares evolution, biology and mechanism of action of all known ABC proteins, including the first structural studies as well as clinical implications. It will be useful to anyone trying to stay abreast of the latest findings. This book is sure to become a classic and will regularly be updated. - Phylogeny and Evoloution of ABC Transporters - Fundamental Aspects of the Mechanism of Action of ABC Transporters - Prokaryote ABC Transporters - Non-Mammalian Transporters - Multidrug Transporters - ABC Transporters, Physiological Roles and Human Disease - Full color throughout
Download or read book Functional Expression of ATP binding Cassette ABC Transporters in Brain Cellular Compartments and in Glial Cells Exposed to HIV 1 Viral Proteins written by Patrick Thomas Ronaldson and published by . This book was released on 2007 with total page 700 pages. Available in PDF, EPUB and Kindle. Book excerpt: Limited drug penetration is an obstacle that is often encountered in the treatment of central nervous system (CNS) diseases including human immunodeficiency virus type-1 (HIV-1) encephalitis (HIVE). ATP-binding cassette (ABC) drug efflux transporter expression [i.e. P-glycoprotein (P-gp), Multidrug Resistance-Associated Protein-1 (Mrp1)] at brain barrier sites and HIV-1 brain cellular targets (i.e., microglia, astrocytes) may represent one mechanism that can restrict CNS permeation of antiretroviral drugs [i.e. HIV-1 protease inhibitors (PIs)]. Furthermore, astrocytes may be activated by viral proteins (i.e., HIV-1 envelope glycoprotein gp120) to produce and secrete toxic substances such as cytokines. However, it is currently unknown if gp120 or cytokine exposure can alter the functional expression of ABC transporters in astrocytes. The overall intent of this Ph. D. project was (i) to investigate P-gp involvement in the transport of PIs, (ii) to examine the cellular/subcellular localization and functional expression of P-gp in astrocytes, (iii) to characterize an in vitro model of HIVE-associated immunological events by treating cultured astrocytes with gp120 and (iv) to investigate ABC transporter expression and activity in cultured astrocytes triggered with gp120 or cytokines. We demonstrated that PIs (i.e., saquinavir, indinavir) are substrates and inhibitors of P-gp in brain cell culture systems. We also showed that P-gp is functionally expressed in cultured human and rodent astrocytes. Furthermore, we detected P-gp localization at the plasma membrane as well as along the nuclear envelope, in cytoplasmic vesicles, and in caveolae. Biochemical studies demonstrated increased cytokine mRNA and protein expression in gp120-treated astrocyte cultures, suggesting in vitro activation of immune responses. Following gp120 exposure, we demonstrated decreased P-gp molecular (i.e., mRNA, protein) expression and drug transport activity. In contrast, Mrp1 mRNA and protein expression as well as efflux activity were increased after gp120 treatment. In addition, saquinavir accumulation was significantly enhanced in gp120-treated astrocytes, which implies that altered transporter activity may lead to changes in brain permeation and distribution of PIs. Cytokine treatment showed that P-gp and Mrp1 protein expression were increased by TNF-alpha while P-gp was decreased by IL-6. Taken together, these data suggest that complex drug-transporter interactions may occur during immune responses associated with HIVE.
Download or read book ABC Transporters Biochemical Cellular and Molecular Aspects written by Suresh V. Ambudkar and published by Gulf Professional Publishing. This book was released on 1998-07-31 with total page 902 pages. Available in PDF, EPUB and Kindle. Book excerpt: The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. More than 285 volumes have been published (all of them still in print) and much of the material is relevant even today-truly an essential publication for researchersin all fields of life sciences. Prokaryotic ABC Transporters Eukaryotic ABC Transporters Nonmammalian ABC Transport Systems Mammalian P-Glycoproteins Multidrug Resistance Associated Protein Cystic Fibrosis Transmembrane Conductance Regulator Sulfonylurea Receptor Intracellular ABC Transporters
Download or read book Behavioral Genetics of the Fly Drosophila Melanogaster written by Josh Dubnau and published by Cambridge University Press. This book was released on 2014-06-26 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: A comprehensive portrayal of the behaviour genetics of the fruit fly (Drosophila melanogaster) and the methods used in these studies.
Download or read book Phase II Conjugation Enzymes and Transport Systems written by Helmut Sies and published by Gulf Professional Publishing. This book was released on 2005-11-28 with total page 774 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume on conjugation enzymes and transporters serves to bring together current methods and concepts in an interesting, important and rapidly developing field of cell and systems biology. Phase II Conjugation Enzymes and Transport Systems focuses on the so-called Phase II enzymes of drug metabolism (xenobiotics), which has important ramifications for endogenous metabolism and nutrition. Also included are aspects on Phase III, transport systems. This volume of Methods in Enzymology presents current knowledge and methodology on glucuronidation, sulfation, acetylation, and transport systems in this field of research. Together with the volumes on Quinones and Quinone Enzymes (volumes 378 and 382), and on Glutathione Transferases and gamma-Glutamyl Transpeptidases (volume 401), the state of knowledge on proteomics and metabolomics of many pathways of (waste) product elimination, enzyme protein induction and gene regulation and feedback control is provided. This volume will help stimulate future investigations and speed the advance of knowledge in systems biology. A laboratory standard for more than 40 years Over 400 volumes strong Also available on ScienceDirect
Download or read book Zinc Biochemistry Physiology and Homeostasis written by W. Maret and published by Springer Science & Business Media. This book was released on 2013-11-11 with total page 232 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chapters in this book review the remarkable advances in the field of zinc biology over the last decade. Zinc is essential for life, in particular for growth and development, through its role in hundreds of zinc enzymes and thousands of zinc proteins. Its catalytic, structural, and regulatory functions in these proteins impact metabolism, gene expression, and signal transduction, including neurotransmission. Among the micronutrients, zinc may rank with iron as to its importance for public health. The topics covered range from single molecules to cells and to whole organisms: the chemistry, design, and application of fluorophores for the determination of cellular zinc; the role of zinc in proliferation, differentiation, and apoptosis of cells; proteins that transport, sense, and distribute zinc and together form a cellular homeostatic system; the coordination chemistry of zinc in metalloproteins; the role of zinc in the brain as a neuromodulator/transmitter; the dependence of the immune system on zinc; zinc homeostasis in the whole human body.
Download or read book ABC Transporters 40 Years on written by Anthony M. George and published by Springer. This book was released on 2015-12-16 with total page 384 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides new structural, biochemical, and clinical information on ABC transporters. The authors explore and describe the state of the art of research, knowledge, and prospects for the future for this important family of proteins. The first ABC transporter was discovered in 1973 and was named P-glycoprotein. It elicits resistance to cytotoxic drugs, chiefly in human tumours, within which chemotherapy failure is observed in about 50% of cases. Together with its complex pharmacology, and even a suspected role in Alzheimer’s disease, this ABC transporter still eludes a clinical solution to its multidrug resistance property. ABC transporters are integral membrane active proteins and they belong to one of the largest protein families across all species. Their myriad roles encompass the import or export of a diverse range of allocrites, including ion, nutrients, peptides, polysaccharides, lipids, and xenobiotics. They are of major medical importance with many members elaborating multidrug resistance in bacteria, fungi, yeast, parasites, and humans. Other ABC transporters are involved in a number of inherited diseases, including cystic fibrosis, macular degeneration, gout, and several other metabolic disorders
Download or read book Plant derived Natural Products written by Anne E. Osbourn and published by Springer Science & Business Media. This book was released on 2009-07-07 with total page 588 pages. Available in PDF, EPUB and Kindle. Book excerpt: Plants produce a huge array of natural products (secondary metabolites). These compounds have important ecological functions, providing protection against attack by herbivores and microbes and serving as attractants for pollinators and seed-dispersing agents. They may also contribute to competition and invasiveness by suppressing the growth of neighboring plant species (a phenomenon known as allelopathy). Humans exploit natural products as sources of drugs, flavoring agents, fragrances and for a wide range of other applications. Rapid progress has been made in recent years in understanding natural product synthesis, regulation and function and the evolution of metabolic diversity. It is timely to bring this information together with contemporary advances in chemistry, plant biology, ecology, agronomy and human health to provide a comprehensive guide to plant-derived natural products. Plant-derived natural products: synthesis, function and application provides an informative and accessible overview of the different facets of the field, ranging from an introduction to the different classes of natural products through developments in natural product chemistry and biology to ecological interactions and the significance of plant-derived natural products for humans. In the final section of the book a series of chapters on new trends covers metabolic engineering, genome-wide approaches, the metabolic consequences of genetic modification, developments in traditional medicines and nutraceuticals, natural products as leads for drug discovery and novel non-food crops.
Download or read book Transporters in Drug Discovery and Development written by Yurong Lai and published by Woodhead Publishing. This book was released on 2014-08-22 with total page 759 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by a leading researcher in the field, Transporters in Drug Discovery and Development provides a comprehensive and practical guide to drug transporter families that are the most important for drug discovery and development. It covers: an overview of transporter families and organ distribution; clinical relevant drug-drug interaction; clinical relevant polymorphism; drug transporter related pharmacokinetic, pharmacodynamics and toxicity; in vitro/in vivo probes of drug transport studies; the practical methodologies of industrial transporter screening and translational aspect in drug discovery and developments. - A comprehensive overview of drug transporter families and their clinical relevance in drug discovery and development - Balanced coverage of molecular biology aspects and functional outcomes - State of art knowledge related to transporter-mediated DDI and the clinical relevance in pharmacokinetics, dynamics, and toxicity
Download or read book MicroRNAs written by Krishnarao Appasani and published by Cambridge University Press. This book was released on 2009-08-20 with total page 580 pages. Available in PDF, EPUB and Kindle. Book excerpt: MicroRNAs (miRNAs) are RNA molecules, conserved by evolution, that regulate gene expressions and their recent discovery is revolutionising both basic biomedical research and drug discovery. Expression levels of MiRNAs have been found to vary between tissues and with developmental stages and hence evaluation of the global expression of miRNAs potentially provides opportunities to identify regulatory points for many different biological processes. This wide-ranging reference work, written by leading experts from both academia and industry, will be an invaluable resource for all those wishing to use miRNA techniques in their own research, from graduate students, post-docs and researchers in academia to those working in R&D in biotechnology and pharmaceutical companies who need to understand this emerging technology. From the discovery of miRNAs and their functions to their detection and role in disease biology, this volume uniquely integrates the basic science with industry application towards drug validation, diagnostic and therapeutic development. Forewords by: Sidney Altman, Yale University, Winner of the Nobel Prize in Chemistry, 1989 and Victor R. Ambros, Dartmouth Medical School, Co-discoverer of MicroRNAs
