Disease relevance of Ddc

• Significant increases in the number of lung adenomas in A/J mice were induced by multiple i.p. injections of cis-DDP and each of the DDCP and SHP complexes (total doses, 21 to 108 mumol/kg body weight) [1].
• Similar treatments with cis-DDP caused a significant increase in the number of skin papillomas in female CD-1 mice given promoting treatments with croton oil; the DDCP and SHP complexes had little or no activity in this system [1].
• The SHP complexes were the most reactive toward DNA and produced a greater reduction in the transforming activity of Bacillus subtilis DNA after 3-hr reaction times than did the DDP or DDCP complexes [1].
• Our goal is to utilize antagonists of the serotonin-producing enzymes (tryptophan hydroxylase and AADC) as the basis for a chemotherapeutic approach to the treatment of carcinoid tumors, a rare tumor type characterized by the overproduction of serotonin [2].
• Human L-Dopa decarboxylase (L-aromatic amino acid decarboxylase, DDC) has been purified from pheochromocytoma tissue, a benign tumor of the catecholamine-synthesizing cells of the adrenal medulla [3].

Psychiatry related information on Ddc

• DDC caused only transient amnesia for passive avoidance training, while the amnestic effect of ANI remained constant at 24-hr and 1-week retention tests [4].

High impact information on Ddc

• There was significant antitumor activity against the neuroblastoma, which was enhanced by combination with a dopa decarboxylase inhibitor, Ro4-4602 [5].
• The results indicate that a distinguishing feature of poor-prognosis NE tumors is a glutamic acid decarboxylase-independent pathway for production of GABA and a pathway for production of imidazole-4-acetate that involves dopa decarboxylase and a membrane-associated amine oxidase, amiloride-binding protein 1 [6].
• The amino acid sequence shows a high degree of similarity with the aromatic L-amino acid decarboxylase (dopa decarboxylase) and the alpha-methyldopa-hypersensitive protein of Drosophila melanogaster [7].
• Some cells from cultured embryonic mouse hypothalamus were found to express aromatic-L-amino acid decarboxylase (EC 4.1.1.28) activity and serotonin uptake and storage [8].
• Endocrine cells of the embryonic pancreas also contain dopa decarboxylase but not dopamine-beta-hydroxylase or phenylethanolamine-N-methyl transferase [9].

Chemical compound and disease context of Ddc

• The influence of several chelating agents (CaDTPA, ZnDTPA, CaEDTA, ZnEDTA, DMSA, D-penicillamine and DMPS, DMP and DDC) on the acute toxicity of CdCl2 and on the whole body retention and tissue distribution of cadmium after the IV application of 115mCdCl2 was compared in mice [10].
• The carcinoid neoplasm is marked by excessive serotonin, synthesized by the conversion of tryptophan (Trp) to 5-hydroxytryptophan by tryptophan hydroxylase (TPH) (EC 1.14.16.4) and decarboxylation of 5-hydroxytryptophan by aromatic-L-amino acid decarboxylase (AAAD) (EC 4.1.1.28) [11].
• OBJECTIVE: Previously we have formulated a new cationic liposome, DDC, composed of dioleoyltrimethylamino propane (DOTAP), 1,2-dioeoyl-3-phosphophatidylethanolamine (DOPE), and cholesterol (Chol), and it efficiently delivered plasmid DNA into ovarian cancer cells [12].
• Exogenous L-DOPA enhances dopamine metabolism in the intact and denervated striatum, and is the treatment of choice for Parkinsonism. Aromatic L-amino acid decarboxylase (AAAD) converts L-DOPA to dopamine [13].
• 2',3'-Dideoxycytidine (DDC), a potent inhibitor of human immunodeficiency virus (HIV), is presently undergoing clinical trials as a promising anti-AIDS drug [14].

Biological context of Ddc

• The fact that neither AADC nor the dopamine transporter could be visualized suggests of non-dopaminergic transmitter phenotype, but the levels of these two dopaminergic markers may be too low to be detected with the present methodology [15].
• Distribution of aromatic L-amino acid decarboxylase mRNA in mouse brain by in situ hybridization histology [16].
• We found that acinar cell precursors express AADC prior to the appearance of an exocrine marker and that the expression of AADC in acinar cells persists throughout embryogenesis to the first month of postnatal life [17].
• We investigated whether the downregulation of the enzyme aromatic l-amino acid decarboxylase (AADC) or the TH cofactor tetrahydrobiopterin (BH4) could account for the loss of catecholamines in these neurons [18].
• Despite of the fact that the impact of various stressful stimuli on catecholamine biosynthetic enzyme gene expression, activity and immunoreactive protein has been intensively studied, less is known about the aromatic L-amino acid decarboxylase (AADC), the enzyme, which catalyzes decarboxylation of L-dihydroxyphenylalanine to dopamine [19].

Anatomical context of Ddc

• AADC activity was greater in the adrenal gland and the cerebellum in the hamster than in the mouse or rat [20].
• Specifically, in the hamster but not the rat or mouse, AADC immunoreactive cells were observed in the cerebellum and adrenal cortex [20].
• Moreover, AADC and VMAT2 are deregulated in midbrain DA cells of Nurr1 knockout embryos as revealed by in situ hybridization [21].
• We also found that exocrine cells containing AADC never express other islet-cell markers [17].
• Enhanced expression of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in cerebellar Purkinje cells of mouse after hyperosmotic stimuli [22].

Associations of Ddc with chemical compounds

• Aromatic L-amino acid decarboxylase (AAAD) is the second enzyme in the sequence leading to the synthesis of catecholamines or serotonin [16].
• Aromatic L-amino acid decarboxylase (AADC), the enzyme that converts L-dopa to dopamine, displayed species-specific differences in both activity and immunoreactivity in the cerebellum, olfactory bulb, and adrenal glands of three rodent species, the hamster, rat, and mouse [20].
• Drinking 2% sodium chloride for 2 weeks resulted in an increase in the number of TH- or AADC-positive Purkinje cells in the caudal vermis, paraflocculus and flocculus of the cerebellum [22].
• This partial cDNA shows 90% identity with mammalian GAD 65 and presents the Asn-Pro-His-Lys (NPHK) sequence corresponding to the pyridoxal-binding region of porcine DOPA decarboxylase or mammalian GAD [23].
• The dopamine D1 receptor family (D1-like) antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benazepine (SCH 23390), elevated aromatic L-amino acid decarboxylase activity and protein content in striatum, as well as the mRNA for the enzyme in midbrain [24].

Regulatory relationships of Ddc

• Expanded ES NP-derived TH(+) neurons coexpressed additional DA markers such as dopa decarboxylase and DAT (dopamine transporter) [25].

Other interactions of Ddc

• In contrast, juxtaglomerular cells in the rat displayed a similar intensity of immunostaining for both AADC and TH [20].
• To address this problem, the expression of DAT, VMAT2 and AADC was analysed at embryonic day 12.5 and 14 [26].
• The mouse homologues, Ddc and Cobl, which map to the homologous imprinted region on proximal Chr 11, were also biallelically expressed in mice with uniparental maternal or paternal inheritance of this region [27].
• Species-specific distribution of aromatic L-amino acid decarboxylase in the rodent adrenal gland, cerebellum, and olfactory bulb [20].
• These neurons contained aromatic L-amino acid decarboxylase as well as TH, NSE and neurofilament immunoreactivities [28].

Analytical, diagnostic and therapeutic context of Ddc

• Antisense riboprobes for aromatic L-amino acid decarboxylase mRNA were used to map the gene in mouse brain by in situ hybridization [16].
• We also tested the hypothesis, whether single or repeated immobilization stress can affect the AADC mRNA or immunoprotein levels in mice stellate ganglia [19].
• DOPA was measured in the anterior pituitary and hypothalamic-hypophysial portal blood after treatment with NSD-1015, a DOPA decarboxylase inhibitor [29].
• Plasmid DNA (pp53-EGFP) and DDC complexes were transfected into ovarian carcinoma cells (OVCAR-3 cells) and gene expression was determined by reverse transcription-polymerase chain reaction and Western blot analysis [12].
• Immunocytochemistry for AADC may become an additional tool not only to highlight APUD cells in tissue sections but also to differentiate the sites of cellular amine synthesis from those of amine storage [30].

References