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1.
[Sitosterolemia (phytosterolemia)].
Lütjohann, D
Der Internist. 2019;(8):871-877
Abstract
Sitosterolemia or phytosterolemia is a rare autosomal recessive hereditary lipid storage disorder. It is caused by homozygous or compound heterozygous mutations in one of the two ABCG5 and ABCG8 genes encoding the intestinal and hepatic heterodimer ABCG5 (sterolin 1)/ABCG8 (sterolin 2) efflux transporters. These mutations lead to intestinal hyperabsorption and reduced hepatic secretion of cholesterol and plant sterols with subsequent accumulation of phytosterols and cholesterol in plasma and deposition in tissue (xanthoma). Phytosterols are found mainly in vegetable oils, margarine, nuts, grains, soybeans and avocados. Patients with sitosterolemia show extreme phenotypic heterogeneity from almost asymptomatic individuals to those with combined severe hypercholesterolemia at a young age, leading to increased atherosclerosis and premature cardiac death. Early abnormalities include hemolytic anemia with stomatocytosis, macrothrombocytopenia and splenomegaly. In addition to strict avoidance of phytosterol-containing foods, the use of the sterol absorption inhibitor ezetimibe, possibly in combination with the bile acid-binding resin cholestyramine, is the most effective treatment option.
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2.
The oligopeptide ABC-importers are essential communication channels in Gram-positive bacteria.
Slamti, L, Lereclus, D
Research in microbiology. 2019;(8):338-344
Abstract
The transport of peptides in microorganisms plays an important role in their physiology and behavior, both as a nutrient source and as a proxy to sense their environment. This latter function is evidenced in Gram-positive bacteria where cell-cell communication is mediated by small peptides. Here, we highlight the importance of the oligopeptide permease (Opp) systems in the various major processes controlled by signaling peptides, such as sporulation, virulence and conjugation. We underline that the functioning of these communication systems is tightly linked to the developmental status of the bacteria via the regulation of opp gene expression by transition phase regulators.
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3.
The SUF system: an ABC ATPase-dependent protein complex with a role in Fe-S cluster biogenesis.
Garcia, PS, Gribaldo, S, Py, B, Barras, F
Research in microbiology. 2019;(8):426-434
Abstract
Iron-sulfur (Fe-S) clusters are considered one of the most ancient and versatile inorganic cofactors present in the three domains of life. Fe-S clusters can act as redox sensors or catalysts and are found to be used by a large number of functional and structurally diverse proteins. Here, we cover current knowledge of the SUF multiprotein machinery that synthesizes and inserts Fe-S clusters into proteins. Specific focus is put on the ABC ATPase SufC, which contributes to building Fe-S clusters, and appeared early on during evolution.
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4.
Holding-Oriented versus Gating-Oriented Live-Cell Distinction: Highlighting the Role of Transporters in Cell Imaging Probe Development.
Choi, YK, Kim, JJ, Chang, YT
Accounts of chemical research. 2019;(11):3097-3107
Abstract
Small molecule imaging probes are powerful tools to understand complex biological systems. The mainstreams of imaging probe developments have been focused on the target holding of the probes; the holding targets are often cell-type-specific biomarkers. This type of the probe mechanism can be designated as holding-oriented live-cell distinction (HOLD). Our group has worked on the development of cell-type-selective probes using a diversity-oriented fluorescence library approach (DOFLA), where unbiased phenotypic screening is employed using fluorescent library compounds. Through the conventional target identification methods such as an affinity-based analysis, we elucidated that some of the probe mechanisms are HOLD. However, we also realized that sometimes there is no specific holding target for probes or the holding targets are ubiquitous. The observation led us to test an alternative mechanism of cell-type-specific probes as gating-oriented live-cell distinction (GOLD). We started to examine the gating mechanism of probes, which is mainly based on transporters but which does not necessarily require probe holding to cellular targets. Transporters can control the in and out movement of various nutrients and chemicals. Different expression levels of transporters in various cell types could provide the molecular mechanism of differential staining of cells by regulating the intracellular accumulation of a certain specific probe. A number of GOLD probes have been developed by modifying or mimicking endogenous substrates of transporters such as inorganic ions, glucose, amino acids, or neurotransmitters, utilizing broad substrate specificity of transporters. The radiolabeled or fluorophore-conjugated substrate mimetics have been widely used for live cell distinction and various applications such as disease-related cell or tissue imaging. In humans, there are about 400 solute carrier (SLC) transporters and 50 ATP-binding cassette (ABC) transporters. Since some transporters have broad substrate specificity, they can transport not only derivatives of endogenous natural substrates but also totally synthetic diverse imaging probes, such as DOFLA probes. Without preconsidering the structure of endogenous substrates, we recently demonstrated a series of live-cell imaging probes and elucidated their molecular mechanism as a gating one, either by SLC or ABC transporters. Transporter inhibitor panel and CRISPR-based transporter libraries could provide a systematic gating target elucidation platform. Considering the generality of DOFLA and the CRISPR-based genomic tool for transporter systems (>450 in humans), the GOLD approach will offer new insight and promise for unprecedented levels of novel cell imaging probe development.
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5.
The Abc of Phosphonate Breakdown: A Mechanism for Bacterial Survival.
Manav, MC, Sofos, N, Hove-Jensen, B, Brodersen, DE
BioEssays : news and reviews in molecular, cellular and developmental biology. 2018;(11):e1800091
Abstract
Bacteria have evolved advanced strategies for surviving during nutritional stress, including expression of specialized enzyme systems that allow them to grow on unusual nutrient sources. Inorganic phosphate (Pi ) is limiting in most ecosystems, hence organisms have developed a sophisticated, enzymatic machinery known as carbon-phosphorus (C-P) lyase, allowing them to extract phosphate from a wide range of phosphonate compounds. These are characterized by a stable covalent bond between carbon and phosphorus making them very hard to break down. Despite the challenges involved in both synthesizing and catabolizing phosphonates, they are widespread in nature. The enzymes required for the bacterial C-P lyase pathway have been identified and for the most part structurally characterized. Nevertheless, the mechanistic principles governing breakdown of phosphonate compounds remain enigmatic. In this review, an overview of the C-P lyase pathway is provided and structural aspects of the involved enzyme complexes are discussed with a special emphasis on the role of ATP-binding cassette (ABC) proteins.
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6.
Functions of ABC transporters in plant growth and development.
Do, THT, Martinoia, E, Lee, Y
Current opinion in plant biology. 2018;:32-38
Abstract
ABC transporters are essential for plant development, playing roles in processes such as gametogenesis, seed development, seed germination, organ formation, and secondary growth. ABC transporters are directly energized by ATP and can transport complex organic materials against concentration gradients; thus, they are uniquely suited to provide the complex building blocks required for the development of specialized plant cells. We review recent progress in our understanding of the contribution ABC transporters make to the growth and development of plants, including their roles in protective layer formation and in transporting phytohormones.
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7.
Effect of Oxidative Stress on ABC Transporters: Contribution to Epilepsy Pharmacoresistance.
Grewal, GK, Kukal, S, Kanojia, N, Saso, L, Kukreti, S, Kukreti, R
Molecules (Basel, Switzerland). 2017;(3)
Abstract
Epilepsy is a neurological disorder affecting around 1%-2% of population worldwide and its treatment includes use of antiepileptic drugs to control seizures. Failure to respond to antiepileptic drug therapy is a major clinical problem and over expression of ATP-binding cassette transporters is considered one of the major reasons for pharmacoresistance. In this review, we have summarized the regulation of ABC transporters in response to oxidative stress due to disease and antiepileptic drugs. Further, ketogenic diet and antioxidants were examined for their role in pharmacoresistance. The understanding of signalling pathways and mechanism involved may help in identifying potential therapeutic targets and improving drug response.
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8.
A Critical View on ABC Transporters and Their Interacting Partners in Auxin Transport.
Geisler, M, Aryal, B, di Donato, M, Hao, P
Plant & cell physiology. 2017;(10):1601-1614
Abstract
Different subclasses of ATP-binding cassette (ABC) transporters have been implicated in the transport of native variants of the phytohormone auxin. Here, the putative, individual roles of key members belonging to the ABCB, ABCD and ABCG families, respectively, are highlighted and the knowledge of their assumed expression and transport routes is reviewed and compared with their mutant phenotypes. Protein-protein interactions between ABC transporters and regulatory components during auxin transport are summarized and their importance is critically discussed. There is a focus on the functional interaction between members of the ABCB family and the FKBP42, TWISTED DWARF1, acting as a chaperone during plasma membrane trafficking of ABCBs. Further, the mode and relevance of functional ABCB-PIN interactions is diagnostically re-evaluated. A new nomenclature describing precisely the most likely ABCB-PIN interaction scenarios is suggested. Finally, available tools for the detection and prediction of ABC transporter interactomes are summarized and the potential of future ABC transporter interactome maps is highlighted.
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9.
Experimenal studies On cell and gene therapies for retinal dystrophies with a particular focus On ABCA4 retinopathies.
Sciezynska, A, Ozieblo, D, Oldak, M
Klinika oczna. 2016;(1):66-71
Abstract
Retinal dystrophies lead to gradual irreversible vision deterioration. The ABCA4 retinopathies constitute an important group of retinal dystrophies. However, there are no effective therapies available for this group of diseases. Yet, with the advent of Molecular therapies, the development of prospective therapeutic approaches seems feasible. The paper summarizes recent advances in gene and cell therapy that may be implemented in retinal dystrophies, especially in ABCA4-associated diseases.
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10.
Modulation of Expression and Activity of ABC Transporters by the Phytoestrogen Genistein. Impact on Drug Disposition.
Rigalli, JP, Ciriaci, N, Mottino, AD, Catania, VA, Ruiz, ML
Current medicinal chemistry. 2016;(13):1370-89
Abstract
ATP binding cassette (ABC) transporters are involved in drug absorption, distribution and elimination. They also mediate multidrug resistance in cancer cells. Isoflavones, such as genistein (GNT), belong to a class of naturally-occurring compounds found at high concentrations in commonly consumed soya based-foods and dietary supplements. GNT and its metabolites interact with ABC transporters as substrates, inhibitors and/or modulators of their expression. This review compiles information about regulation of ABC transporters by GNT with special emphasis on the three major groups of ABC transporters involved in excretion of endo- and xenobiotics as follows: Pglycoprotein (MDR1, ABCB1), a group of multidrug resistance associated proteins (MRPs, ABCC subfamily) and ABCG2 (BCRP), an ABC half-transporter. The impact of these regulations on potential GNT-drug interactions is further considered.