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Specific Transporters (specific + transporter)
Selected AbstractsCharacterization of the myo -inositol transport system in Trypanosoma cruziFEBS JOURNAL, Issue 9 2000Marcelo Einicker-Lamas myo -Inositol is a growth factor for mammalian cells as well as for the pathogenic protozoa Trypanosoma cruzi. Most of the cell surface molecules in this organism rely on myo -inositol as the biosynthetic precursor for phosphoinositides and glycosylated phosphatidylinositols. The aim of this work was to investigate the process of myo -inositol translocation across the parasite cell membrane. myo -Inositol uptake was concentration-dependent in the concentration range 0.1,10 µm with maximal transport obtained at 8 µm. Using sodium-free buffers, where Na+ was replaced by choline or K+, myo -inositol uptake was inhibited by 50%. Furosemide, an inhibitor of the ouabain-insensitive Na+ -ATPase, inhibited the Na+ -dependent and Na+ -independent myo -inositol uptake by 68 and 33%, respectively. In contrast, ouabain, an (Na++/K+) ATPase inhibitor, did not affect transport. Part of the myo -inositol uptake is mediated by active transport as it was inhibited when energy metabolism inhibitors such as carbonyl cyanide p -(trifluoromethoxy)-phenylhydrazone (34%), 2,4-dinitrophenol (50%), KCN (71%) and NaN3 (69%) were added to the medium, or the temperature of the medium was lowered to 4 °C. The addition of glucose (5,50 mm) or mannose (10 mm) did not change the myo -inositol uptake, whereas the addition of 10 mm nonlabeled myo -inositol totally inhibited this transport, indicating that the transporter is specific for myo -inositol. Phloretin (0.3 mm) and phoridzin (5 mm), but not cytochalasin B, were efficient inhibitors of myo -inositol uptake. A portion of the accumulated myo -inositol is converted to inositol phosphates and phosphoinositides. These data show that myo -inositol transport in T. cruzi epimastigotes is mediated by at least two specific transporters , one Na+ -dependent and the other Na+ -independent. [source] The inflammatory cytokine, interleukin-1 beta, mediates loss of astroglial glutamate transport and drives excitotoxic motor neuron injury in the spinal cord during acute viral encephalomyelitisJOURNAL OF NEUROCHEMISTRY, Issue 4 2008Natalie A. Prow Abstract Astrocytes remove glutamate from the synaptic cleft via specific transporters, and impaired glutamate reuptake may promote excitotoxic neuronal injury. In a model of viral encephalomyelitis caused by neuroadapted Sindbis virus (NSV), mice develop acute paralysis and spinal motor neuron degeneration inhibited by the AMPA receptor antagonist, NBQX. To investigate disrupted glutamate homeostasis in the spinal cord, expression of the main astroglial glutamate transporter, GLT-1, was examined. GLT-1 levels declined in the spinal cord during acute infection while GFAP expression was preserved. There was simultaneous production of inflammatory cytokines at this site, and susceptible animals treated with drugs that blocked IL-1, release also limited paralysis and prevented the loss of GLT-1 expression. Conversely, infection of resistant mice that develop mild paralysis following NSV challenge showed higher baseline GLT-1 levels as well as lower production of IL-1, and relatively preserved GLT-1 expression in the spinal cord compared to susceptible hosts. Finally, spinal cord GLT-1 expression was largely maintained following infection of IL-1,-deficient animals. Together, these data show that IL-1, inhibits astrocyte glutamate transport in the spinal cord during viral encephalomyelitis. They provide one of the strongest in vivo links between innate immune responses and the development of excitotoxicity demonstrated to date. [source] Fast food delivery: the response of nursing astrocytes to an exciting call from neuronsJOURNAL OF NEUROCHEMISTRY, Issue 2003L. Pellerin It was suggested long time ago that astrocytes might play a prominent role in the distribution of energy substrates to neurons but convincing evidence was lacking. More recently, the excitatory neurotransmitter glutamate was shown to enhance aerobic glycolysis in cultured cortical astrocytes by a mechanism involving glial glutamate transporters. Using specific knockout mice for these transporters, it was demonstrated that a classical metabolic response to neuronal activation in the whisker-to-barrel system, 2-deoxyglucose accumulation, was disrupted in the somatosensory cortex of these animals at postnatal day 10. From these data, it was concluded that a net transfer of some energy substrate, preferentially lactate, must be taking place in order to fulfill increasing neuronal energy needs during periods of enhanced activity. In support of this concept, the presence of specific transporters for lactate, known as monocarboxylate transporters, was recently described both on astrocytes and neurons in vitro as well as in vivo. [source] Structure, function, and regulation of renal organic anion transportersMEDICINAL RESEARCH REVIEWS, Issue 6 2002Guofeng You Abstract Renal elimination of anionic drugs, xenobiotics, and toxins is necessary for the survival of mammalian species. This process is mediated by vectorial transport from blood to urine through the cooperative functions of specific transporters in the basolateral and apical membranes of the proximal tubule epithelium. The first step of this process is the extraction of organic anions from the peritubular blood plasma into proximal tubule cells largely through the organic anion transporter (OAT) pathway. Therefore, the OAT pathway is one of the major sites for body drug clearance/detoxification. As a result, it is also the site for drug,drug interaction and drug-induced nephrotoxicity. To maximize therapeutic efficacy and minimize toxicity, the structure-function relationships of OATs and their regulation must be defined. The recent cloning and identification of OATs have paved the way for such investigations. This review summarizes the available data on the general properties of OATs, focusing in particular on the recent progress made from the author's laboratory as well as from other's, on the molecular characterization of the structure-function relationships of OATs and their regulatory mechanisms. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 6, 602,616, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10019 [source] Development of the blood-brain barrier: A historical point of viewTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2006Domenico Ribatti Abstract Although there has been considerable controversy since the observation by Ehrlich more than 100 years ago that the brain did not take up dyes from the vascular system, the concept of an endothelial blood-brain barrier (BBB) was confirmed by the unequivocal demonstration that the passage of molecules from blood to brain and vice versa was prevented by endothelial tight junctions (TJs). There are three major functions implicated in the term "BBB": protection of the brain from the blood milieu, selective transport, and metabolism or modification of blood- or brain-borne substances. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of complex TJs and a number of specific transport and enzyme systems that regulate molecular traffic across the endothelial cells. The development of the BBB is a complex process that leads to endothelial cells with unique permeability characteristics due to high electrical resistance and the expression of specific transporters and metabolic pathways. This review article summarizes the historical background underlying our current knowledge of the cellular and molecular mechanisms involved in the development and maintenance of the BBB. Anat Rec (Part B: New Anat) 289B:3,8, 2006. © 2006 Wiley-Liss, Inc. [source] | |||||||||||||