Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TYROSINE DECARBOXYLASE”

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 1,333 records · Page 74Linked to original sources

3,4-Dihydroxyphenylalanine (dopa) decarboxylase activity in the arthropod nervous system.

1. When homogenates of brains from mature adult locusts (Locusta migratoria) were incubated with l-3-(3,4-dihydroxyphenyl)[3-(14)C]alanine the major radioactive metabolite was dopamine, suggesting the presence of a dopa (3,4-dihydroxyphenylalanine) decarboxylase. 2. Decarboxylation of l-dopa by this tissue, measured under optimum conditions by a radiochemical method, was 21mumol of CO(2)/h per g wet wt. Apparent decarboxylation of l-tyrosine proceeded at 0.34mumol of CO(2)/h per g wet wt. There was no detectable decarboxylation of l-tryptophan, l-histidine or l-phenylalanine. 3. Dopa decarboxylase activity was found in all major regions of the ventral nerve cord of the mature locust (range: 4-7mumol of CO(2)/h per g wet wt.) but was low or absent in thoracic peripheral nerve. 4. Marked decarboxylation of l-dopa was found in homogenates of brains of four other species of insects, and in brain and ventral nerve cord, but not in the claw nerve, of the crayfish. 5. The activity of the locust brain enzyme may be slightly lower at the time of imaginal ecdysis than during the mature period. By contrast, the dopa decarboxylase that produces dopamine as an intermediate in cuticle biosynthesis is known to be high in activity at the time of ecdysis and low in activity during the intermoult stages.

Animals↗

Vesicular autoantigens of type 1 diabetes.

Type 1 diabetes, also referred to as insulin-dependent diabetes mellitus (IDDM), is an autoimmune disorder resulting from the destruction of pancreatic beta-cells and insulin deficiency. In the last 10 years significant progress has been made in this field, primarily because of the identification of predisposing genes, the extensive investigation of animal models, and the characterization of major autoantigens. This review draws attention to how the study of beta-cell autoantigens may contribute insight into the pathogenesis of IDDM and provides an update on the cell biology of glutamic acid decarboxylase (GAD) and islet cell autoantigen 512, two major targets of autoimmunity in Type 1 diabetes on which I have focused my efforts. For reasons of space I have mostly considered here studies on GAD which have been published since 1994.

Amino Acid Sequence↗

Number of autoantibodies (against insulin, GAD or ICA512/IA2) rather than particular autoantibody specificities determines risk of type I diabetes.

We previously evaluated radioassays for insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GAA) and ICA512bdc autoantibodies (ICA512bdcAA) in the prediction of type I diabetes. Among first degree relatives, the five year risk of diabetes was 0% if no autoantibody was positive, 15% if only one was positive, 44% if two were positive and 100% if all three were positive. We measured IAA, GAA and ICA512bdcAA in 45 patients with new onset type I diabetes (sampled within 7 days of insulin therapy), 882 first degree relatives of patients with type I diabetes, and 217 control subjects. ICA512bdc is a construct of the ICA512/IA2 molecule (amino acid residues 256-979), including the intracellular domain. Based on receiver-operating characteristic plots, there was no significant difference between the three assays in their ability to discriminate between disease and control subjects. The upper limits of normal for the assays were determined as the 99th percentile of levels in the control subjects or higher. Using these cut-offs, 76% of new onset patients were positive for two or more autoantibodies, and 98% were positive for one or more. In comparison, none of 198 control subjects tested for all three assays were positive for more than one autoantibody. In relatives with a single autoantibody, or exactly two autoantibodies, there was no difference in diabetes-free survival according to which one of the autoantibodies was present (P = 0.70, logrank test), or which particular combination of autoantibodies was present (P = 0.56, logrank test) respectively. Our conclusions were as follows: the number of autoantibodies (counting IAA, GAA and ICA512bdcAA) is important in prediction, rather than the particular autoantibody specificities present. Among patients with new onset insulin-dependent diabetes, the absence of any of these autoantibodies justifies the consideration of non-autoimmune forms of diabetes in the differential diagnosis.

Adolescent↗

Impaired dopamine function and muscular rigidity induced by 6-aminonicotinamide in rats.

In corpus striatum, 6-aminonicotinamide (6-AN), 10 mg/kg i.p. lowered the concentration of dopamine and markedly reduced the disappearance of dopamine after synthesis inhibition with alpha-methyl-p-tyrosine. In the dopamine-rich part of the limbic system, the formation of DOPA after decarboxylase inhibition with 3-hydroxybenzylhydrazine was decreased. In diencephalon, 6-AN altered neither the steady-state level nor the utilization of noradrenaline. The data suggest that the muscular rigidity induced by 6-AN may be associated with disruption of dopaminergic transmission.

6-Aminonicotinamide↗

Neurochemical studies in a mouse teratoma with neuroepithelial differentiation. Presence of cyclic AMP, serotonin and enzymes of the serotonergic, adrenergic and cholinergic systems.

A transplantable mouse testicular teratoma (OTT 6050) which displays a spectrum of neuroepithelial differentiation was evaluated biochemically for concentrations of cyclic AMP (cAMP), serotonin (5-HT), and enzymes involved in the metabolism of the biogenic amines and acetylcholine. These values were compared between teratomas with neuroepithelial differentiation as the major or minor component and brains of neonatal and adult mice of related strains. cAMP, 5-HT, tryptophan hydroxylase (TPH), aromatic amino acid decarboxylase (AADC) and monoamine oxidase (MAO) were present. In addition, enzymes of the adrenergic system, i.e. tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DBH), and of the cholinergic system, i.e. choline acetyltransferase and acetylcholinesterase, were studied. Biochemical differences in tumor groups probably reflected variations in the proportion of neuroepithelial components: trends suggested an increase of cAMP and an increased activity of TPH, AADC, TH and DBH in tumors with increased proportions of neuroepithelial cells. These findings indicate that the neuroepithelial component of the mouse teratoma may serve as a model for the study of neuronal differentiation in primitive neuroepithelial neoplasms.

Acetylcholinesterase↗

Reduction of GABAergic transmission and alterations in behavior after 6-OHDA treatment of rats.

We studied the effects of neonatal administration of 6-hydroxydopamine (6-OHDA) upon gamma-aminobutyric acid (GABA) and noradrenergic neurotransmission in the developing rat brain. After 6-OHDA administration tyrosine hydroxylase (TH) immunolabelling revealed more than 70% loss of catecholaminergic terminals in cortex. Glutamic acid decarboxylase (GAD) immunolabelling showed that the intensity of staining and the density of labelled terminals were decreased by approximately 50% in the prefrontal cortex of 6-OHDA treated animals, but in visual and somatosensory zones there was no difference between lesioned and control cortex. The open field test revealed an altered development of the searching activity after neonatal 6-OHDA injections. A significant difference was found between 6-OHDA treated and control rats in searching, orienting and skills performance. Our results indicate that the behavioral changes observed in young rats after 6-OHDA treatment may be reflections not only of reduced catecholaminergic transmission but also of GABAergic disturbance, occurring in the frontal cortex.

Animals↗

The insulin-dependent diabetes mellitus-associated ICA 105 autoantigen in stiff-man syndrome patients.

The pathogenetic role of anti-glutamic acid decarboxylase (GAD) antibodies found in up to 60% of patients with stiff-man syndrome (SMS) is still controversial. GAD, in fact, is also one of the major target antigen of insulin-dependent diabetes mellitus (IDDM), a disease affecting one third of anti-GAD antibody-positive patients with SMS. To better define the role of autoimmunity in SMS we looked for molecular and immunological evidence of an autoimmune recognition of a second IDDM-associated autoantigen, the pancreatic 37/40 kDa IDDM-autoantigen, whose gene called ICA 105 has been recently cloned. By Northern blot analysis we found that tissue distribution of human ICA 105 is restricted to pancreas and brain and within the central nervous system (CNS) its distribution is similar to GAD. We also measured anti-ICA 105 antibodies in 11 SMS patients and 56 control patients with other neurological diseases (OND). Anti-ICA 105 antibodies were found in 4/11 (36%) patients with SMS (a frequency similar to that of anti-GAD-antibodies in our SMS population) but in only 2/56 (3%) patients with OND (P < 0.001). Anti-ICA 105 and anti-GAD antibodies were associated in 3/4 (75%) patients with SMS but in none of the 2 anti-ICA 105 antibody-positive OND patients. Among anti-ICA 105 antibody-positive patients with SMS, only 1 suffered also from IDDM. In contrast, the only 2 anti-ICA 105 antibody-positive with OND had IDDM. Our results indicate that ICA 105 represents another putative neuroendocrine autoantigen in SMS. The presence of circulating anti-GAD and/or anti-ICA 105 antibodies might help the diagnosis of SMS. The absence, however, of antibodies recognising specific CNS autoantigens (e.g. GAD, ICA 105) does not rule out SMS.

Adult↗

Sensitive non-isotopic assays for autoantibodies to IA-2 and to a combination of both IA-2 and GAD65.

BACKGROUND: A sensitive ELISA for measurement of IA-2 autoantibodies has been developed and assessed. Also, a combination ELISA for detection of both GAD65 autoantibodies and IA-2 autoantibodies is described. METHODS: The IA-2 autoantibody assay is based on the ability of IA-2 autoantibodies to form a bridge between IA-2 intracellular fragment coated onto ELISA plate wells and liquid-phase IA-2 labelled with biotin. The combination ELISA uses plates coated with both IA-2 and GAD65 and a mixture of IA-2-biotin and GAD65-biotin. Assay sensitivity was assessed using the WHO reference (NIBSC 97/550) for islet cell antibodies. IA-2 autoantibody measurements by ELISA were compared with measurements in immunoprecipitation assays (IPAs) based on 125I or 35S labelled IA-2. Combination ELISA results were compared with results obtained for individual autoantibodies. RESULTS: As little as 15 units/mL of NIBSC 97/550 was detectable in the IA-2 autoantibody ELISA compared to 125 units/mL by 125I-IA-2 IPA. 110/216(51%) sera from patients with type 1 DM were positive in the IA-2 autoantibody ELISA while 97/216 (45%) and 91/216 (42%) were positive in the 125I-IA2 and 35S-IA-2 IPAs, respectively. The IA-2 autoantibody ELISA showed 100% specificity for type 1 DM. The combination ELISA was able to detect GAD65 and/or IA-2 autoantibodies in 183/216 (85%) diabetic sera and 183/216 (85%) were also found positive for autoantibodies to IA-2 and/or to GAD65 in the assays for individual antibodies. Autoantibody measurements in the individual autoantibody assays and in the combination ELISA showed good agreement by Pearson correlation (r=0.92, n=216, p<0.001) and by Bland and Altman analysis. CONCLUSIONS: Sensitive and specific ELISAs for measurement of autoantibodies to IA-2 and to a combination of IA-2 and GAD65 have been developed. These assays are suitable for screening large numbers of samples in diabetes prediction and prevention trials.

Antibody Specificity↗