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Glutamate Metabolism (glutamate + metabolism)
Selected AbstractsGlutamine synthetase enhances the clearance of extracellular glutamate by the neural retinaJOURNAL OF NEUROCHEMISTRY, Issue 3 2002Iftach Shaked Abstract Clearance of synaptic glutamate by glial cells is required for the normal function of excitatory synapses and for prevention of neurotoxicity. Although the regulatory role of glial glutamate transporters in glutamate clearance is well established, little is known about the influence of glial glutamate metabolism on this process. This study examines whether glutamine synthetase (GS), a glial-specific enzyme that amidates glutamate to glutamine, affects the uptake of glutamate. Retinal explants were incubated in the presence of [14C]glutamate and glutamate uptake was assessed by measurement of the amount of radioactively labeled molecules within the cells and the amount of [14C]glutamine released to the medium. An increase in GS expression in Müller glial cells, caused by induction of the endogenous gene, did not affect the amount of glutamate accumulated within the cells, but led to a dramatic increase in the amount of glutamine released. This increase, which was directly correlated with the level of GS expression, was dependent on the presence of external sodium ions, and could be completely abolished by methionine sulfoximine, a specific inhibitor of GS activity. Our results demonstrate that GS activity significantly influences the uptake of glutamate by the neural retina and suggest that this enzyme may represent an important target for neuroprotective strategies. [source] Proteomic Analysis Demonstrates Adolescent Vulnerability to Lasting Hippocampal Changes Following Chronic Alcohol ConsumptionALCOHOLISM, Issue 1 2009Garth A. Hargreaves Background:, Excessive teenage alcohol consumption is of great concern because alcohol may adversely alter the developmental trajectory of the brain. The aim of the present study was to assess whether chronic intermittent alcohol intake during the adolescent period alters hippocampal protein expression to a greater extent than during adulthood. Methods:, Adolescent [postnatal day (PND) 27] and adult (PND 55) male Wistar rats were given 8 hours daily access to beer (4.44% ethanol v/v) in addition to ad libitum food and water for 4 weeks. From a large subject pool, subgroups of adolescent and adult rats were selected that displayed equivalent alcohol intake (average of 6.1 g/kg/day ethanol). The 4 weeks of alcohol access were followed by a 2-week alcohol-free washout period after which the hippocampus was analyzed using 2-DE proteomics. Results:, Beer consumption by the adult group resulted in modest hippocampal changes relative to alcohol naïve adult controls. The only changes observed were an up-regulation of citrate synthase (a precursor to the Krebs cycle) and fatty acid binding protein (which facilitates fatty acid metabolism). In contrast, adolescent rats consuming alcohol showed more widespread hippocampal changes relative to adolescent controls. These included an increase in cytoskeletal protein T-complex protein 1 subunit epsilon (TCP-1) and a decrease in the expression of 10 other proteins, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), triose phosphate isomerise, alpha-enolase, and phosphoglycerate kinase 1 (all involved in glycolysis); glutamate dehydrogenase 1 (an important regulator of glutamate); methylmalonate-semialdehyde dehydrogenase (involved in aldehyde detoxification); ubiquitin carboxyl-terminal hydrolase isozyme L1 (a regulator of protein degradation); and synapsin 2 (involved in synaptogenesis and neurotransmitter release). Conclusions:, These results suggest the adolescent hippocampus is more vulnerable to lasting proteomic changes following repeated alcohol exposure. The proteins most affected include those related to glycolysis, glutamate metabolism, neurodegeneration, synaptic function, and cytoskeletal structure. [source] Expression of neuronal markers, synaptic proteins, and glutamine synthetase in the control and regenerating lizard visual systemTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 19 2010M.M. Romero-Alemán Abstract Spontaneous regrowth of retinal ganglion cell (RGC) axons occurs after optic nerve (ON) transection in the lizard Gallotia galloti. To gain more insight into this event we performed an immunohistochemical study on selected neuron and glial markers, which proved useful for analyzing the axonal regrowth process in different regeneration models. In the control lizards, RGCs were beta-III tubulin- (Tuj1) and HuCD-positive. The vesicular glutamate transporter-1 (VGLUT1) preferentially stained RGCs and glial somata rather than synaptic layers. In contrast, SV2 and vesicular GABA/glycine transporter (VGAT) labeling was restricted to both plexiform layers. Strikingly, the strong expression of glutamine synthetase (GS) in both Müller glia processes and macroglial somata revealed a high glutamate metabolism along the visual system. Upregulation of Tuj1 and HuCD in the surviving RGCs was observed at all the timepoints studied (1, 3, 6, 9, and 12 months postlesion). The significant rise of Tuj1 in the optic nerve head and optic tract (OTr) by 1 and 6 months postlesion, respectively, suggests an increase of the beta-III tubulin transport and incorporation into newly formed axons. Persistent Tuj1+ and SV2+ puncta and swellings were abnormally observed in putative degenerating/dystrophic fibers. Unexpectedly, neuron-like cells of obscure significance were identified in the control and regenerating ON-OTr. We conclude that: 1) the persistent upregulation of Tuj1 and HuCD favors the long-lasting axonal regrowth process; 2) the latter succeeded despite the ectopia and dystrophy of some regrowing fibers; and 3) maintenance of the glutamate-glutamine cycle contributes to the homeostasis and plasticity of the system. J. Comp. Neurol. 518:4067,4087, 2010. © 2010 Wiley-Liss, Inc. [source] Type 1 diabetes: can exercise impair the autoimmune event?CELL BIOCHEMISTRY AND FUNCTION, Issue 4 2008The L -arginine/glutamine coupling hypothesis Abstract Prevention of type 1 diabetes mellitus (T1DM) requires early intervention in the autoimmune process directed against ,-cells of the pancreatic islets of Langerhans, which is believed to result from a disorder of immunoregulation. According to this concept, a T-helper lymphocyte of type 1 (Th1) subset of T-lymphocytes and their cytokine products, the type 1 cytokines [e.g. interleukin 2 (IL-2), interferon gamma (IFN-,) and tumour necrosis factor beta (TNF-,)] prevail over immunoregulatory (anti-inflammatory) Th2 subset and its cytokine products, i.e. type 2 cytokines (e.g. IL-4, IL-6 and IL-10). This allows type 1 cytokines to initiate a cascade of immune/inflammatory processes in the islet (insulitis), culminating in ,-cell destruction. Activation of sympathetic-corticotropin-releasing hormone (CRH) axis by psychological stress induces specifically Th1 cell overactivity that determines enhanced glutamine utilization and consequent poor L -arginine supply for nitric oxide (NO)-assisted insulin secretion. This determines the shift of intraislet glutamate metabolism from the synthesis of glutathione (GSH) to that of L -arginine, leading to a redox imbalance that activates nuclear factor ,B exacerbating inflammation and NO-mediated cytotoxicity. Physical exercise is capable of inducing changes in the pattern of cytokine production and release towards type 2 class and to normalize the glutamine supply to the circulation, which reduces the need for glutamate, whose metabolic fate may be restored in the direction of GSH synthesis and antioxidant defence. Also, the 70-kDa heat shock protein (hsp70), which is immunoregulatory, may modulate exercise-induced anti-inflammation. In this work, we envisage how exercise can intervene in the mechanisms involved in the autoimmune process against ,-cells and how novel therapeutic approaches may be inferred from these observations. Copyright © 2008 John Wiley & Sons, Ltd. [source] | ||||||||||