Disease relevance of DDC

• On the other hand, bronchial carcinoids and lung PDNECs showed high DDC mRNA levels, but nearly undetectable HDC mRNA levels [1].
• TH activity was high in the controls and was markedly decreased, in substantia nigra, caudate nucleus, putamen and in pallidum, in all three cases of Parkinsonism. DDC activity in these regions was also decreased in 2 patients [2].
• However, the tyrosine hydroxylase, AADC and DBH mRNA concentrations in the pheochromocytomas were greater than those of the normal adrenal medullas [3].
• Histidine decarboxylase, DOPA decarboxylase, and vesicular monoamine transporter 2 expression in neuroendocrine tumors: immunohistochemical study and gene expression analysis [1].
• CONCLUSION: The triple transduction of TH, AADC and GCH genes with separate AAV vectors is effective, which might be important to gene therapy for Parkinson's disease [4].

Psychiatry related information on DDC

• Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND) [5].
• Thus, our results do not support an involvement of the 1-bp or 4-bp deletion within the DDC gene in the etiology of affective disorders [6].
• No association between polymorphisms in the DDC gene and paranoid schizophrenia in a northern Chinese population [7].
• Application of juvenile hormone I showed that the critical period for determination of the level of the later increase in DDC activity was about 4 hr after head capsule slippage at the peak of the ecdysteroid titer [8].
• Dopa-decarboxylase, acetylcholinesterase, sodium plus potassium stimulated adenosine triphosphatase (Na+ + K+-ATPase), and membrane-bound protein kinase were compared in the erythrocytes of patients with Huntington's disease and normal controls [9].

High impact information on DDC

• A low ratio indicates decreased dopa decarboxylase activity and dopamine storage [10].
• Bromocriptine in high doses (up to 100 mg per day) was administered to 14 patients with advanced Parkinson's disease whose disorder was progressing despite optimum treatment with levodopa combined with a peripheral dopa decarboxylase inhibitor (carbidopa) [11].
• However, levels of DOPA decarboxylase and the vesicular monoamine transporter, known to be reduced in Parkinson's disease, were normal [12].
• All cell lines contained tyrosine hydroxylase, aromatic L-amino acid decarboxylase, and dopamine-beta-hydroxylase [13].
• There was no statistically significant difference with respect to clinical improvement or deterioration in patients treated with either L-dopa or L-dopa and dopa-decarboxylase inhibitor or placebo [14].

Chemical compound and disease context of DDC

• A highly sensitive molecular method was used to evaluate the presence of dopamine decarboxylase (DDC) mRNA in the bone marrow and peripheral blood of patients with neuroblastoma (NB) [15].
• Systolic orthostatic hypotension was observed in only one patient during the control test, but it occurred more frequently after L-Dopa/DDC inhibitor, regardless of concomitant administration of either entacapone (n = 3) or placebo (n = 4) [16].
• CONCLUSIONS: The efficacy and tolerability of entacapone administered with levodopa/AADC inhibitor have not yet been compared with those of other strategies for the treatment of Parkinson's disease [17].
• We have compared the effects of entacapone, a peripherally acting catechol-O-methyltransferase (COMT) inhibitor, and placebo on cardiovascular autonomic responses in L-Dopa/dopa decarboxylase inhibitor-treated patients with Parkinson's disease (PD) [16].
• Together, our data demonstrate that DDC interacts with AR to enhance steroid receptor transactivation, which may have important implications in prostate cancer progression [18].

Biological context of DDC

• Western blotting analysis showed a cross-reaction between anti-HDC and anti-DDC antibodies [1].
• Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence [5].
• The present study investigated two Danish families for linkage between manic depressive illness, a marker at the DDC locus which has been mapped to 7p11-p13 and 10 microsatellite markers covering chromosome 7q11-p15 [19].
• Our results demonstrate the detection of a new alternative splicing event within the coding region of the human DDC mRNA, further suggesting that the single copy human DDC gene undergoes complex processing leading to the formation of multiple mRNA isoforms [20].
• In this report, we describe a novel splice variant of DDC mRNA in human tissue, lacking exons 10-15 of the full-length transcript but including an alternative exon 10 [20].

Anatomical context of DDC

• The AADC activities, measured with L-DOPA as the substrate, increased from 114 pmol/min mg in the corpus to 3488 pmol/min mg in the jejunum [21].
• COMT activities varied between 40-350 pmol/mg/min and AADC activities between 100-3300 pmol/mg/min in different parts of the gastrointestinal tract [22].
• A comparison of PAM activity and DDC levels in 30 lung cancer cell lines indicated that peptide amidating activity may be an indicator of NE status [23].
• The results with TTMS and AIA, but not with 4-ethyl DDC, were the same in individual human enzymes expressed in Supersomes and human liver microsomes [24].
• The number of AADC-positive neurons was especially large in the ventral striatum including the nucleus accumbens [25].

Associations of DDC with chemical compounds

• Since the endogenous AADC activity in the striatum is considered to be low, coexpression of both TH and AADC in the same striatal cells would increase the dopamine production and thereby augment the therapeutic effects [26].
• AADC neurons in the human ACC might transform L-DOPA to dopamine, droxidopa to noradrenaline, and/or 5-hydroxytryptophan to serotonin [27].
• Three Types of Tyrosine Hydroxylase-Positive CNS Neurons Distinguished by Dopa Decarboxylase and VMAT2 Co-Expression [28].
• L-dopa as substrate for human duodenal catechol-O-methyltransferase and aromatic L-amino acid decarboxylase [22].
• In vitro carbidopa inhibited AADC slightly more effectively than benserazide [22].

Physical interactions of DDC

• Winged helix hepatocyte nuclear factor 3 and POU-domain protein brn-2/N-oct-3 bind overlapping sites on the neuronal promoter of human aromatic L-amino acid decarboxylase gene [29].

Regulatory relationships of DDC

• In addition, dual immunofluorescence analysis revealed that approximately 55% of the mixed population of DDC- and chromogranin A-expressing NE cells continue to express AR [30].
• This suggests that in the early stage of nigrostriatal dopamine neurone degeneration, DDC levels may be less susceptible to neurodegenerative influences than is TH synthesis or, alternatively, DDC synthesis may be more aggressively upregulated [31].
• Glucocorticoid receptor activity was also strongly enhanced with DDC co-transfection, while oestrogen receptor activity was only mildly affected [18].
• As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2) [32].
• LC and DDC migrated as mature/activated APC able to stimulate allogeneic naive CD4+ T cells and to induce memory Th1 cells in the absence of IL-12p70 [33].

Other interactions of DDC

• Immunostaining showed that TH and AADC were coexpressed efficiently in the same striatal cells in vitro and in vivo [26].
• The assays of activities and function of TH, AADC, and GCH1 and their potential use in ex vivo gene therapy of PD [34].
• Western blotting analysis was performed to verify the specificity of anti-DDC and anti-HDC antibodies [1].
• The increased mRNA levels of TH and AADC were maintained at 48 h, whereas the level of DBH mRNA was sharply decreased at 48 h [35].
• DDC demonstrated a low level of selectivity as an inhibitory probe for chlorzoxazone 6-hydroxylation (CYP2E1-mediated) [36].

Analytical, diagnostic and therapeutic context of DDC

• Real-time RT-PCR was performed using specific probes for HDC and DDC on 42 cases, examined also for DDC IR [1].
• These results suggest that GCH, in addition to TH and AADC, is important for effective gene therapy of PD [37].
• We examined the distribution of striatal D-neurons using AADC immunohistochemistry and postmortem brains obtained by legal and pathological autopsies (nine controls (27-75 years old) and nine schizophrenics (32-78 years old), postmortem interval to fixation (PMI): 2-30 h) [38].
• In this study we show the expression of DDC in human placental tissue and present data on the molecular cloning and in vitro expression of the active recombinant enzyme [39].
• Northern blot analysis indicated that the alt-DDC transcript is expressed in high levels in human kidney [20].

References