Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLUTAMIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,513 records · Page 84Linked to original sources
PubMed1981

The release of gamma-aminobutyric acid, glutamate, and acetylcholine from striatal slices: a mass fragmentographic study.

The release processes of endogenous Acetylcholine (ACh), gamma-aminobutyric acid (GABA), glutamate (Glu) and glutamine (GLN) were studied in superfused guinea-pig caudatal slices. Basal ACh release remained constant for up to 2 h, while the basal release of GABA, Glu and GLN declined to half or less of its initial values after 1 h of superfusion. Electrical stimulation increased the ACh release by 700-800% and that of GABA by 80% whereas it decreased the output of Glu by 50% and failed to modify the GLN efflux. KCl (25 nM) increased the output of ACh by 400%, that of GABA by approximately 500% and decreased that of Glu by 40%. Substituting of CaCl(2) by MgCl(2) in the superfusion medium reduced the basal efflux of GABA, Glu and GLN. Under these conditions, no evoked release of ACh or of GABA was detected, following electrical or KCl stimulation. Tetrodotoxin 5 x 10(-7) decreased the basal ACh release by 60% and increased the GABA efflux by 40%. The toxin abolished the stimulus-evoked ACh efflux but scarcely affected that of GABA. These results are consistent with a possible neurotransmitter role of ACh and GABA in the striatum and show some differences in the ionic mechanisms underlying GABA and ACh release.

Acetylcholine↗
PubMed1998

Characterization of novel T-cell epitopes on 65 kDa and 67 kDa glutamic acid decarboxylase relevant in autoimmune responses in NOD mice.

It has recently been shown that the T-cell mediated immune responses to glutamic acid decarboxylase (GAD) play an important role in insulin-dependent diabetes mellitus (IDDM) in NOD mice. However, specific epitopes responsible for eliciting these responses remain unresolved. In this study, the T-cell epitopes involved in GAD-specific immune responses in NOD mice were characterized. By priming NOD mice with GAD65, three new GAD65 epitopes (GAD65 78-97, GAD65 202-221, GAD65 217-236) distinct from those previously reported were found. Furthermore, our investigations into the fine determinant specificity of GAD67 revealed two additional GAD67-specific peptide epitopes (GAD67 28-47, GAD67 42-61). Two of the GAD65 epitopes (GAD65 202-221 and GAD65 217-236) are shared between GAD65 and GAD67. Spontaneous immune responses to these peptides were found in pre-diabetic and diabetic mice and differential patterns of responses to these peptides were observed depending on the age of the mice, disease status, or if the mice were protected from diabetes by adjuvant immunotherapy. Characterization of these new epitopes will help in the elucidation of autoimmune responses to GAD in IDDM.

Age Factors↗
PubMed1986

Identification of an essential glutamic acid residue in beta-lactamase II from Bacillus cereus.

Beta-Lactamase II from Bacillus cereus was readily inactivated by incubation at pH 4.75 with a water-soluble carbodiimide plus a suitable nucleophile. In the early stages of the reaction, 1 equivalent of nucleophile was incorporated/equivalent of enzyme, whereas during the later stages a second equivalent of nucleophile was also incorporated. This latter process correlated with the blocking of the enzyme's single thiol group. Enzyme inactivated in the presence of the coloured nucleophile N-(2,4-dinitrophenyl)ethylenediamine was fragmented by pepsin digestion, and coloured peptides were isolated by gel filtration and h.p.l.c. Two major peptides, representing 52% of the incorporated label, were isolated and sequenced. Both peptides contained the incorporated label on glutamic acid-37, and it is concluded that this latter residue represents a catalytically essential carboxylic residue in beta-lactamase II.

Bacillus cereus↗
PubMed1982

Surface properties of kidney brushborder membranes affecting the transport of glutamic acid.

The uptake of 14C-glu by rat renal brushborder membrane vesicles was assayed in the presence of transmembrane ionic gradients for the purpose of characterizing surface properties which influence the transport process. Preincubation of membranes with the cationic protein lysozyme led to a significant decrease in transport activity. Similar results were obtained with polylysine and lysine. Polycations such as lysozyme and polylysine were capable of aggregating membrane vesicles whereas lysine was ineffective. Neither aggregation nor membrane injury provided an explanation for the depression of 14C-glu transport. The cationic drug harmaline at a concentration of 2.5 mM significantly reduced sodium dependent 14C-glu uptake provided drug and membranes were pre-equilibrated prior to the transport assay. Using an indirect spectrophotometric method to estimate harmaline concentrations, no evidence was obtained for strong harmaline binding to the membrane. The effect of harmaline could be eliminated by washing membranes in drug-free buffer or diluting membranes in larger volumes of sodium chloride. Membranes pretreated with the lectin Concanavalin A or the enzyme neuraminidase transported glu at control rates, but the proteolytic enzyme papain markedly impaired the transport function without altering mean vesicle volume. The optimal temperature for the assay was 30 degrees C. No temperature discontinuities in the Arrhenius plot of glu transport rates were found between 5 and 30 degrees C. These results with glutamic acid differ from data reported by other investigators on the transport characteristics of glucose and neutral amino acids by brushborder membrane vesicles. The results enhance the possibility that dicarboxylic acid binding proteins may be present on the luminal surface of proximal tubular epithelium.

Animals↗
PubMed2001

Targeting of the transcription factor Max during apoptosis: phosphorylation-regulated cleavage by caspase-5 at an unusual glutamic acid residue in position P1.

Max is the central component of the Myc/Max/Mad network of transcription factors that regulate growth, differentiation and apoptosis. Whereas the Myc and Mad genes and proteins are highly regulated, Max expression is constitutive and no post-translational regulation is known. We have found that Max is targeted during Fas-induced apoptosis. Max is first dephosphorylated and subsequently cleaved by caspases. Two specific cleavage sites for caspases in Max were identified, one at IEVE(10) decreasing S and one at SAFD(135) decreasing G near the C-terminus, which are cleaved in vitro by caspase-5 and caspase-7 respectively. Mutational analysis indicates that both sites are also used in vivo. Thus Max represents the first caspase-5 substrate. The unusual cleavage after a glutamic acid residue is observed only with full-length, DNA-binding competent Max protein but not with corresponding peptides, suggesting that structural determinants might be important for this activity. Furthermore, cleavage by caspase-5 is inhibited by the protein kinase CK2-mediated phosphorylation of Max at Ser-11, a previously mapped phosphorylation site in vivo. These findings suggest that Fas-mediated dephosphorylation of Max is required for cleavage by caspase-5. The modifications that occur on Max in response to Fas signalling affect the DNA-binding activity of Max/Max homodimers. Taken together, our findings uncover three distinct processes, namely dephosphorylation and cleavage by caspase-5 and caspase-7, that target Max during Fas-mediated apoptosis, suggesting the regulation of the Myc/Max/Mad network through its central component.

Amino Acid Chloromethyl Ketones↗
PubMed2005

Autoimmunity to glutamic acid decarboxylase in the neurodegenerative disorder Batten disease.

The pathogenic mechanisms underlying Batten disease are unclear. Patients uniformly possess autoantibodies against glutamic acid decarboxylase (GAD) that are predominantly reactive with a region of GAD (amino acids 1 to 20) distinct from subjects with autoimmune type 1 diabetes or stiff-person syndrome. Batten patients did not possess autoantibodies against other type 1 diabetes-associated autoantigens and human leukocyte antigen genotypes revealed no specific associations with this disease.

Adolescent↗
PubMed1993

A newly recognized point mutation in the cytochrome b558 heavy chain gene replacing alanine57 by glutamic acid, in a patient with cytochrome b positive X-linked chronic granulomatous disease.

Molecular genetic analysis was performed in a patient with cytochrome b positive X-linked chronic granulomatous disease. A previous Southern blot study, using a cytochrome b heavy chain cDNA as probe, revealed a Pst I restriction fragment pattern for the cytochrome b heavy chain gene (CYBB) different to that of normal individuals. Since restriction length polymorphism with Pst I has never been observed in control individuals and no abnormal restriction fragment patterns in the patient's CYBB was detected with seven other enzymes used, we focussed on the single Pst I site in the CYBB cDNA as being the only mutation site responsible for his disease. A fragment of the patient's cDNA which included the Pst I site was amplified by reverse polymerase chain reaction, and loss of the Pst I site in the fragment was confirmed by incubation with Pst I. Subsequent sequence analysis of the fragment revealed a point mutation in the Pst I site (cytosine to adenine), substituting glutamic acid for alanine at position 57.

Alanine↗
PubMed1984

The distribution of glutamic acid decarboxylase immunoreactivity in the diencephalon of the opossum and rabbit.

We have examined the distribution of neurons and terminals immunoreactive for glutamic acid decarboxylase (GAD) in the thalamus and adjacent structures of the opossum (Didelphis virginiana) and the rabbit and have compared this distribution with the distributions we described previously for the cat and bushbaby (Galago senegalensis). The significance of these experiments depends, first, on the fact that GAD is the synthetic enzyme for GABA, and therefore that GAD immunoreactivity is a marker for GABAergic inhibitory neurons, and second, on previous findings that suggest that GABAergic neurons in the dorsal thalamus are local circuit neurons. In both cat and Galago, GAD-immunoreactive neurons are distributed essentially throughout the entire thalamus. In the opossum, GAD neurons are chiefly confined to the dorsal lateral geniculate nucleus and the lateral extremity of the lateral posterior nucleus. The distribution of GAD neurons in the rabbit is intermediate between that found in the opossum on the one hand and cat and Galago on the other. Like opossum, about 25% of the neurons in the lateral geniculate nucleus of rabbit are GAD immunoreactive. Unlike opossum, however, as many as 18% of the cells in the ventral posterior nucleus of the rabbit are GAD immunoreactive, and scattered cells are also labeled in other thalamic areas, such as the medial geniculate and the lateral group. Aside from the findings in the dorsal thalamus, the chief observation is that GAD-immunoreactive neurons and/or terminals densely fill all principal targets of the optic tract, including the ventral lateral geniculate nucleus; the superficial gray layer of the superior colliculus; the anterior, posterior, and olivary pretectal nuclei; the nucleus of the optic tract; and the medial and lateral terminal nuclei of the accessory optic tract. These results support the idea first put forward by Cajal that local circuit neurons increase in number during the course of the evolution of complex mammalian brains. If we can assume that the conservative opossum retains characteristics reflecting an early stage of mammalian evolution, the results suggest that thalamic local circuit neurons arose first in the visual system and only later in evolution spread throughout the thalamus.

Animals↗
PubMed1996

Glutamic acid decarboxylase autoantibodies in stiff-man syndrome and insulin-dependent diabetes mellitus exhibit similarities and differences in epitope recognition.

Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS). However, most individuals with one of these diseases do not have the other disease. Prior studies have suggested that the natures of the GAD Abs associated with each of these diseases are different, which may have implications for the autoimmune pathogenesis. We have compared the GAD autoantibody profile and have mapped GAD protein epitope regions in the two diseases using an immunoprecipitation assay with recombinant GAD 65 and GAD 67 proteins, GAD protein fragments, and synthetic GAD peptides, as well as chimeric GAD proteins. Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM. The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563. These types of GAD Abs are not found in IDDM sera. All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65. In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein. These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM. These results indicate that although disease-specific epitopes may exist, there is also overlap in the humoral response between the two diseases.

Autoantibodies↗
PubMed1991

Transplants of fetal substantia nigra regulate glutamic acid decarboxylase gene expression in host striatal neurons.

Lesions of the dopaminergic innervation to the striatum result in increased activity of glutamic acid decarboxylase (GAD) and increased GAD mRNA in striatal GABAergic neurons. Here we show that solid transplants of dopamine-containing fetal mesencephalic tissue placed adjacent to the striatum can completely reverse the elevation of GAD mRNA in the striatum of adult rats with complete lesions of the nigrostriatal dopamine projections. The ability of the fetal transplants to re-establish control over gene expression in host target neurons indicates that there is a significant transneuronal influence of the transplanted neurons. Furthermore, striatal GAD mRNA levels appear to be a good marker of the functional impact of dopamine-producing transplants.

Animals↗
PubMed1999

Immunohistochemical detection of the enzyme glutamic acid decarboxylase and hormones of the islets of Langerhans in spontaneous insulin-dependent diabetes mellitus in cattle.

Immunohistochemical expression of glutamic acid decarboxylase (GAD) enzyme was detected in the pancreatic islets of 12 cattle with spontaneous insulin-dependent diabetes mellitus (IDDM). The most characteristic changes were atrophy and decreased number of pancreatic islets, enlarged islets with vacuolated beta cells, and lymphocytic islet adenitis. Atrophied islets were composed of small islet cells without cytoplasmic insulin-positive granules. Immunohistochemically, GAD was not found in the cytoplasm of atrophied islet cells. Furthermore, enlarged islets consisting of islet cells with vacuolated cytoplasm were frequently observed. The cytoplasm of vacuolated cells contained very few GAD- and insulin-positive granules, indicating beta cell destruction. Enlarged islets with mild lymphocytic infiltrates were frequently observed. These findings suggest that islet cells in cattle with IDDM lose their insulin synthesis function and their ability to regulate hormonal secretion of alpha and delta cells.

Animals↗
PubMed1991

Parallel decrease of glutamic acid decarboxylase and preproenkephalin mRNA in the rat striatum following chronic treatment with a dopaminergic D1 antagonist and D2 agonist.

The levels of mRNA encoding glutamic acid decarboxylase (GAD) and preproenkephalin (PPE) were measured by Northern blot analysis, in the dorsal and the ventral part of the striatum, following long-term treatments with drugs acting selectively on D1 or D2 dopaminergic receptors. Chronic injection of the selective D1 antagonist SCH 23390 elicited a significant decrease in level of both GAD and PPE mRNA (-30%) in the dorsal striatum, whereas no significant change was observed in the ventral striatum. Chronic administration of both SCH 23390 and RU 24926, a D2 agonist, decreased the GAD and PPE mRNA levels in the dorsal (-38 and -57%, respectively) as well as in the ventral (-70 and -60%, respectively) striatum. In the ventral striatum the marked reduction of GAD mRNA levels was paralleled by a significant decrease of Vmax values of GAD enzymatic activity (-41%). These results suggest that the decrease in content of both GAD and PPE mRNA, promoted by the chronic blockade of D1 receptors, is mainly due to the action of dopamine acting on unaffected D2 receptors. Indeed, this decrease is further amplified when the D2 agonist and the D1 antagonist are administered together. Our results substantiate further the molecular mechanisms by which dopamine acts on different populations of GABAergic and enkephalinergic neurons in the two striatal regions examined.

Animals↗
PubMed1989

Neurogenesis of glutamic acid decarboxylase immunoreactive cells in the hippocampus of the mouse. II: Area dentata.

The temporal patterns of neurogenesis of cells showing glutamic acid decarboxylase (GAD) immunoreactivity were determined in the area dentata of the mouse. Pregnant C57Bl mice received pulse injections of (3H)thymidine from E11 through E17 (E0 being the day of mating). The distribution of (3H)thymidine-labeled, GAD-positive neurons in the hilus and in the different strata of the fascia dentata (stratum infragranulosum, stratum granulosum, stratum moleculare) were recorded in adult animals. A radial gradient of neurogenesis of GAD-positive cells in the area dentata was not apparent. In the transverse axis, neurogenesis of GAD-positive cells seemed to follow a faint suprapyramidal to infrapyramidal gradient, which was due to differential timing of neurogenesis of GAD-positive cells destined for the stratum infragranulosum of the suprapyramidal and infrapyramidal blades of the fascia dentata. GABAergic neurons in the fascia dentata comprise a limited number of well-defined cell types. All of the different morphologic types of GAD-positive neurons present in the area dentata were generated prenatally. These diverse forms did not have specific times of neurogenesis. These results support the concept that the adult morphology of GAD-positive cells in the area dentata of the mouse do not bear any relationship to their times of origin.

Animals↗
PubMed1981

Microtopography of tyrosine hydroxylase, glutamic acid decarboxylase, and choline acetyltransferase in the substantia nigra and ventral tegmental area of control and Parkinsonian brains.

Tyrosine hydroxylase (TH), glutamic acid decarboxylase (GAD), and choline acetyl transferase (CAT) were used as markers for catecholamine, gamma-aminobutyric acid, and acetylcholine containing neurons in human mesencephalon. Their rostrocaudal, mediolateral, and dorsoventral distribution was investigated within the substantia nigra pars compacta (SNC) and pars reticulata (SNR) and in the ventral tegmental area (VTA). TH activity was highest in the caudal, medial, and ventral SNC and in the middle of VTA medio-ventrally. The enzyme activity in SNR was low and uniformly distributed. In SNC as well as SNR, GAD activity was high and greater laterally and in the middle of the rostro-caudal extent. No particular pattern of distribution was observed in VTA. an area with low GAD content. In the substantia nigra, CAT activity was low. A characteristic medio-ventral distribution with a peak of high enzyme activity in the middle of the rostrocaudal extent was observed. In VTA, enzyme levels were high and also concentrated medio-ventrally and in the middle of the area. In parkinsonian brains, the distribution of TH was uniformly affected throughout the rostro-caudal extent. In VTA the enzyme activity was not as reduced as in SNC and SNR; the CAT pattern was only disrupted in a very localized part of SNC but not in SNR and VTA. In all three areas, GAD activity was reduced to a uniformly low distribution.

Aged↗
PubMed1992

Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals.

The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin-dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet-cell cytoplasmic auto-antibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell auto-antibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2 = 182, p = 0.0001). None of the relatives with low genetic risk (n = 64), i.e. HLA-different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗