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Yakugaku Zasshi : Journal of the... 2021
Topics: ATP-Binding Cassette Transporters; Drug Discovery; Humans; Membrane Transport Proteins; Nucleotide Transport Proteins; Organic Anion Transporters; Organic Cation Transport Proteins; Research; Sodium-Glucose Transporter 2
PubMed: 33790115
DOI: 10.1248/yakushi.20-00204-F -
Molecules (Basel, Switzerland) Nov 2018Drug transporters mediate the absorption, tissue distribution, and excretion of drugs. The cDNAs of P-glycoprotein, multidrug resistance proteins (MRPs/ABCC), breast... (Review)
Review
Drug transporters mediate the absorption, tissue distribution, and excretion of drugs. The cDNAs of P-glycoprotein, multidrug resistance proteins (MRPs/ABCC), breast cancer resistance protein (BCRP/ABCG2), peptide transporters (PEPTs/SLC15), proton-coupled folate transporters (PCFT/SLC46A1), organic anion transporting polypeptides (OATPs/SLCO), organic anion transporters (OATs/SLC22), organic cation transporters (OCTs/SLC22), and multidrug and toxin extrusions (MATEs/SLC47) have been isolated, and their functions have been elucidated. Enantioselectivity has been demonstrated in the pharmacokinetics and efficacy of drugs, and is important for elucidating the relationship with recognition of drugs by drug transporters from a chiral aspect. Enantioselectivity in the transport of drugs by drug transporters and the inhibitory effects of drugs on drug transporters has been summarized in this review.
Topics: Animals; Humans; Membrane Transport Proteins; Molecular Structure; Pharmaceutical Preparations; Pharmacokinetics; Stereoisomerism; Structure-Activity Relationship; Tissue Distribution
PubMed: 30467304
DOI: 10.3390/molecules23123062 -
Trends in Plant Science Jun 2017Cytokinins are phytohormones essential for cytokinesis and many other physiological and developmental processes in planta. Long-distance transport and intercellular... (Review)
Review
Cytokinins are phytohormones essential for cytokinesis and many other physiological and developmental processes in planta. Long-distance transport and intercellular transport have been postulated. For these processes, the existence of cytokinin transporters has been suggested. Recently, a transporter loading the xylem (AtABCG14) and another for cellular import (AtPUP14) have been discovered. AtABCG14 participates in the xylem loading process of cytokinins and contributes to the positive regulation of shoot growth. The cellular importer AtPUP14 is required to suppress cytokinin signaling. A role of a transporter as stop signal is a new paradigm for a hormone transporter.
Topics: Arabidopsis; Arabidopsis Proteins; Biological Transport; Cytokinins; Membrane Transport Proteins; Signal Transduction
PubMed: 28372884
DOI: 10.1016/j.tplants.2017.03.003 -
Biomolecules Nov 2019Plastids, organelles that evolved from cyanobacteria via endosymbiosis in eukaryotes, provide carbohydrates for the formation of biomass and for mitochondrial energy... (Review)
Review
Plastids, organelles that evolved from cyanobacteria via endosymbiosis in eukaryotes, provide carbohydrates for the formation of biomass and for mitochondrial energy production to the cell. They generate their own energy in the form of the nucleotide adenosine triphosphate (ATP). However, plastids of non-photosynthetic tissues, or during the dark, depend on external supply of ATP. A dedicated antiporter that exchanges ATP against adenosine diphosphate (ADP) plus inorganic phosphate (Pi) takes over this function in most photosynthetic eukaryotes. Additional forms of such nucleotide transporters (NTTs), with deviating activities, are found in intracellular bacteria, and, surprisingly, also in diatoms, a group of algae that acquired their plastids from other eukaryotes via one (or even several) additional endosymbioses compared to algae with primary plastids and higher plants. In this review, we summarize what is known about the nucleotide synthesis and transport pathways in diatom cells, and discuss the evolutionary implications of the presence of the additional NTTs in diatoms, as well as their applications in biotechnology.
Topics: Biological Evolution; Biological Transport; Biotechnology; Diatoms; Membrane Transport Proteins; Nucleotides
PubMed: 31766535
DOI: 10.3390/biom9120761 -
Research in Microbiology 2018The over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) superfamily is one of the main causes of multidrug-resistance (MDR)... (Review)
Review
The over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) superfamily is one of the main causes of multidrug-resistance (MDR) in Gram-negative pathogenic bacteria. AcrB is the most thoroughly studied RND transporter and has functioned as a model for our understanding of efflux-mediated MDR. This multidrug-exporter can recognize and transport a wide range of structurally unrelated compounds (including antibiotics, dyes, bile salts and detergents), while it shows a strict inhibitor specificity. Here we discuss our current knowledge of AcrB, and include recent advances, regarding its structure, mechanism of drug transport, substrate recognition, different intramolecular entry pathways and the drug export driven by remote conformational coupling.
Topics: Animals; Anti-Bacterial Agents; Bacterial Proteins; Biological Transport; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Membrane Transport Proteins
PubMed: 29807096
DOI: 10.1016/j.resmic.2018.05.005 -
The Biochemical Journal Feb 2017Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both... (Review)
Review
Astrocytes play a fundamental role in maintaining the health and function of the central nervous system. Increasing evidence indicates that astrocytes undergo both cellular and molecular changes at an early stage in neurological diseases, including Alzheimer's disease (AD). These changes may reflect a change from a neuroprotective to a neurotoxic phenotype. Given the lack of current disease-modifying therapies for AD, astrocytes have become an interesting and viable target for therapeutic intervention. The astrocyte transport system covers a diverse array of proteins involved in metabolic support, neurotransmission and synaptic architecture. Therefore, specific targeting of individual transporter families has the potential to suppress neurodegeneration, a characteristic hallmark of AD. A small number of the 400 transporter superfamilies are expressed in astrocytes, with evidence highlighting a fraction of these are implicated in AD. Here, we review the current evidence for six astrocytic transporter subfamilies involved in AD, as reported in both animal and human studies. This review confirms that astrocytes are indeed a viable target, highlights the complexities of studying astrocytes and provides future directives to exploit the potential of astrocytes in tackling AD.
Topics: ATP-Binding Cassette Transporters; Alzheimer Disease; Animals; Astrocytes; GABA Plasma Membrane Transport Proteins; Gene Expression Regulation; Glucose Transport Proteins, Facilitative; Glutamate Plasma Membrane Transport Proteins; Glycine Plasma Membrane Transport Proteins; Humans; Membrane Transport Proteins; Multigene Family; Serotonin Plasma Membrane Transport Proteins; Signal Transduction; Sodium-Potassium-Exchanging ATPase
PubMed: 28108584
DOI: 10.1042/BCJ20160505 -
Nature Reviews. Drug Discovery Jan 2015Potential drug-drug interactions mediated by the ATP-binding cassette (ABC) transporter and solute carrier (SLC) transporter families are of clinical and regulatory... (Review)
Review
Potential drug-drug interactions mediated by the ATP-binding cassette (ABC) transporter and solute carrier (SLC) transporter families are of clinical and regulatory concern. However, the endogenous functions of these drug transporters are not well understood. Discussed here is evidence for the roles of ABC and SLC transporters in the handling of diverse substrates, including metabolites, antioxidants, signalling molecules, hormones, nutrients and neurotransmitters. It is suggested that these transporters may be part of a larger system of remote communication ('remote sensing and signalling') between cells, organs, body fluid compartments and perhaps even separate organisms. This broader view may help to clarify disease mechanisms, drug-metabolite interactions and drug effects relevant to diabetes, chronic kidney disease, metabolic syndrome, hypertension, gout, liver disease, neuropsychiatric disorders, inflammatory syndromes and organ injury, as well as prenatal and postnatal development.
Topics: ATP-Binding Cassette Transporters; Animals; Biological Transport; Drug Interactions; Humans; Membrane Transport Proteins; Organic Anion Transporters; Pharmaceutical Preparations
PubMed: 25475361
DOI: 10.1038/nrd4461 -
Current Opinion in Structural Biology Oct 2018The need for bacteria to interact with their environment has driven the evolution of elaborate secretion systems. By virtue of their function, secretion systems are... (Review)
Review
The need for bacteria to interact with their environment has driven the evolution of elaborate secretion systems. By virtue of their function, secretion systems are macromolecular complexes associated with the cell envelope and therefore inherently difficult to study by conventional structural biology techniques. Cryo-electron microscopy (cryoEM) has become an invaluable technique to study large membrane-embedded complexes and led to major advances in the mechanistic understanding of secretion systems. CryoEM comprises of two main modalities, namely single particle analysis and tomography. Here, we review how detailed structures retrieved by single particle analysis combine elegantly with tomography experiments in which the secretion systems are observed in their native cellular context.
Topics: Bacterial Secretion Systems; Cryoelectron Microscopy; Macromolecular Substances; Membrane Transport Proteins; Models, Biological
PubMed: 30223223
DOI: 10.1016/j.sbi.2018.08.007 -
Handbook of Experimental Pharmacology 2018The human genome encodes 19 genes of the solute carrier 6 (SLC6) family; non-synonymous changes in the coding sequence give rise to mutated transporters, which are... (Review)
Review
The human genome encodes 19 genes of the solute carrier 6 (SLC6) family; non-synonymous changes in the coding sequence give rise to mutated transporters, which are misfolded and thus cause diseases in the affected individuals. Prominent examples include mutations in the transporters for dopamine (DAT, SLC6A3), for creatine (CT1, SLC6A8), and for glycine (GlyT2, SLC6A5), which result in infantile dystonia, mental retardation, and hyperekplexia, respectively. Thus, there is an obvious unmet medical need to identify compounds, which can remedy the folding deficit. The pharmacological correction of folding defects was originally explored in mutants of the serotonin transporter (SERT, SLC6A4), which were created to study the COPII-dependent export from the endoplasmic reticulum. This led to the serendipitous discovery of the pharmacochaperoning action of ibogaine. Ibogaine and its metabolite noribogaine also rescue several disease-relevant mutants of DAT. Because the pharmacology of DAT and SERT is exceptionally rich, it is not surprising that additional compounds have been identified, which rescue folding-deficient mutants. These compounds are not only of interest for restoring DAT function in the affected children. They are also likely to serve as useful tools to interrogate the folding trajectory of the transporter. This is likely to initiate a virtuous cycle: if the principles underlying folding of SLC6 transporters are understood, the design of pharmacochaperones ought to be facilitated.
Topics: Animals; Dopamine Plasma Membrane Transport Proteins; Drug Discovery; Humans; Molecular Chaperones; Mutation; Protein Folding; Proteostasis Deficiencies; Serotonin Plasma Membrane Transport Proteins; Solute Carrier Proteins
PubMed: 29086036
DOI: 10.1007/164_2017_71 -
The Journal of Endocrinology Oct 2015Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of... (Review)
Review
Breast cancer is the second most common cancer worldwide and the leading cause of cancer death in women, with incidence rates that continue to rise. The heterogeneity of the disease makes breast cancer exceptionally difficult to treat, particularly for those patients with triple-negative disease. To address the therapeutic complexity of these tumours, new strategies for diagnosis and treatment are urgently required. The ability of lactating and malignant breast cells to uptake and transport iodide has led to the hypothesis that radioiodide therapy could be a potentially viable treatment for many breast cancer patients. Understanding how iodide is transported, and the factors regulating the expression and function of the proteins responsible for iodide transport, is critical for translating this hypothesis into reality. This review covers the three known iodide transporters - the sodium iodide symporter, pendrin and the sodium-coupled monocarboxylate transporter - and their role in iodide transport in breast cells, along with efforts to manipulate them to increase the potential for radioiodide therapy as a treatment for breast cancer.
Topics: Animals; Biological Transport; Breast; Breast Neoplasms; Female; Humans; Iodides; Lactation; Membrane Transport Proteins; Models, Biological; Monocarboxylic Acid Transporters; Neoplasm Proteins; Sulfate Transporters; Symporters
PubMed: 26285906
DOI: 10.1530/JOE-15-0234