DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase))

Florou, Dimitra; Scorilas, Andreas; Vassilacopoulou, Dido; Eg, Fragoulis

doi:10.4267/2042/46069

Cited by 6 publications

(10 citation statements)

References 78 publications

(78 reference statements)

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“…Taking into account that the virus-mediated effects on the DDC protein and mRNA occur with different kinetics, especially in the case of HCV infection, where DDC protein is affected much earlier than the mRNA, we hypothesize that viruses may utilize distinct regulatory mechanisms for DDC. This is not surprising, as DDC expression and function is under the control of complicated and mostly uncharacterized mechanisms [19]. Virus-mediated DDC regulation is dependent, at least in part, on the viral RNA replication stage (Figure 2).…”

Section: Discussionmentioning

confidence: 99%

“…Apart from its expression in the nervous system, where it has a well-established role in neurotransmission, DDC has been purified from various peripheral organs, including the liver [8,9,10,11,12,13,14,15]. Although the physiological function of DDC in the periphery remains unclear [16,17,18], alterations in its expression have been reported in several malignancies such as small-cell lung and gastric cancer [19]. In human placenta, a naturally occurring inhibitor of DDC was identified as Annexin V [20].…”

Section: Introductionmentioning

confidence: 99%

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Emerging Role of l-Dopa Decarboxylase in Flaviviridae Virus Infections

Frakolaki

Kalliampakou

Kaimou

et al. 2019

Cells

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l-dopa decarboxylase (DDC) that catalyzes the biosynthesis of bioactive amines, such as dopamine and serotonin, is expressed in the nervous system and peripheral tissues, including the liver, where its physiological role remains unknown. Recently, we reported a physical and functional interaction of DDC with the major signaling regulator phosphoinosite-3-kinase (PI3K). Here, we provide compelling evidence for the involvement of DDC in viral infections. Studying dengue (DENV) and hepatitis C (HCV) virus infection in hepatocytes and HCV replication in liver samples of infected patients, we observed a negative association between DDC and viral replication. Specifically, replication of both viruses reduced the levels of DDC mRNA and the ~120 kDa SDS-resistant DDC immunoreactive functional complex, concomitant with a PI3K-dependent accumulation of the ~50 kDa DDC monomer. Moreover, viral infection inhibited PI3K-DDC association, while DDC did not colocalize with viral replication sites. DDC overexpression suppressed DENV and HCV RNA replication, while DDC enzymatic inhibition enhanced viral replication and infectivity and affected DENV-induced cell death. Consistently, we observed an inverse correlation between DDC mRNA and HCV RNA levels in liver biopsies from chronically infected patients. These data reveal a novel relationship between DDC and Flaviviridae replication cycle and the role of PI3K in this process.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Emerging Role of l-Dopa Decarboxylase in Flaviviridae Virus Infections

Frakolaki

Kalliampakou

Kaimou

et al. 2019

Cells

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“…After reverse transcription (RT), real-time quantitative PCR (qPCR) was performed in cDNA reactions using the SYBR Green-based Luna 1 Universal qPCR Master Mix (New England Biolabs) as well as primer pairs specific for DDC, ACE2, dACE2, ISG56 and EPO (Table 1), previously validated [5,12,[31][32][33], or the cell type marker genes EPCAM, CD45, CD74 and LYN (S1 Table ). The primers for DDC bind to exons 10 and 12, and detect the majority of the known DDC mRNA isoforms [8,34]. The house-keeping gene 14-3-3-zeta polypeptide (YWHAZ) was used as a normalization control.…”

Section: Rna Quantification By Reverse Transcription-quantitative Pcr (Rt-qpcr)mentioning

confidence: 99%

“…Analysis of a large number of human microarray datasets from various tissues revealed that the L-Dopa decarboxylase (DDC) gene exhibited the most statistically significant co-expression link with ACE2 locus [7]. DDC catalyzes decarboxylation reactions, among them the conversion of L-3,4-dihydroxyphenylalanine (L-Dopa) to the immune-modulatory catecholamine dopamine [8,9] and of 5-hydroxytryptophan to the inflammation and immunity regulator serotonin [10]. Both dopamine and serotonin act also as neurotransmitters providing a linkage between immune and neuron systems [11].…”

Section: Introductionmentioning

confidence: 99%

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

et al. 2021

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L-Dopa decarboxylase (DDC) is the most significantly co-expressed gene with ACE2, which encodes for the SARS-CoV-2 receptor angiotensin-converting enzyme 2 and the interferon-inducible truncated isoform dACE2. Our group previously showed the importance of DDC in viral infections. We hereby aimed to investigate DDC expression in COVID-19 patients and cultured SARS-CoV-2-infected cells, also in association with ACE2 and dACE2. We concurrently evaluated the expression of the viral infection- and interferon-stimulated gene ISG56 and the immune-modulatory, hypoxia-regulated gene EPO. Viral load and mRNA levels of DDC, ACE2, dACE2, ISG56 and EPO were quantified by RT-qPCR in nasopharyngeal swab samples from COVID-19 patients, showing no or mild symptoms, and from non-infected individuals. Samples from influenza-infected patients were analyzed in comparison. SARS-CoV-2-mediated effects in host gene expression were validated in cultured virus-permissive epithelial cells. We found substantially higher gene expression of DDC in COVID-19 patients (7.6-fold; p = 1.2e-13) but not in influenza-infected ones, compared to non-infected subjects. dACE2 was more elevated (2.9-fold; p = 1.02e-16) than ACE2 (1.7-fold; p = 0.0005) in SARS-CoV-2-infected individuals. ISG56 (2.5-fold; p = 3.01e-6) and EPO (2.6-fold; p = 2.1e-13) were also increased. Detected differences were not attributed to enrichment of specific cell populations in nasopharyngeal tissue. While SARS-CoV-2 virus load was positively associated with ACE2 expression (r≥0.8, p<0.001), it negatively correlated with DDC, dACE2 (r≤−0.7, p<0.001) and EPO (r≤−0.5, p<0.05). Moreover, a statistically significant correlation between DDC and dACE2 expression was observed in nasopharyngeal swab and whole blood samples of both COVID-19 and non-infected individuals (r≥0.7). In VeroE6 cells, SARS-CoV-2 negatively affected DDC, ACE2, dACE2 and EPO mRNA levels, and induced cell death, while ISG56 was enhanced at early hours post-infection. Thus, the regulation of DDC, dACE2 and EPO expression in the SARS-CoV-2-infected nasopharyngeal tissue is possibly related with an orchestrated antiviral response of the infected host as the virus suppresses these genes to favor its propagation.

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“…DDC is localized both in the cytosol and cell membrane [ 14 ]. Enzymatically active DDC has already been detected in brain, liver, kidney, adrenal glands, pancreas, cervix [ 15 ], placenta [ 16 ], as well as in peripheral leukocytes and T-cells [ 17 ]. The presence of DDC activity in leukocytes and in the histiocytic lymphoma cell line U-937 implies a cross-talk between the nervous and the immune system, and raises new questions about the regulatory role of DDC in immune responses [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

et al. 2012

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BackgroundHead and neck squamous cell carcinoma (HNSCC) represents one of the most commonly diagnosed malignancies worldwide. The DDC gene encodes L-DOPA decarboxylase, an enzyme catalyzing the decarboxylation of L-DOPA to dopamine. We have recently shown that DDC mRNA is a significant predictor of patients’ prognosis in colorectal adenocarcinoma and prostate cancer. The aim of the current study was to analyze the DDC mRNA expression in HNSCC patients.Methods53 malignant tumors were resected from the larynx, pharynx, tongue, buccal mucosa, parotid glands, and nasal cavity, as well as from 34 adjacent non-cancerous tissues of HNSCC patients, and were homogenized. Total RNA was isolated and converted into first-strand cDNA. An ultrasensitive real-time PCR method based on the SYBR Green chemistry was used for DDC mRNA quantification in head and neck tissue specimens. Relative quantification was performed using the comparative Ct (2-ddCt) method.ResultsDDC mRNA levels were lower in squamous cell carcinomas (SCCs) of the larynx and tongue than in adjacent non-cancerous tissue specimens. Furthermore, low DDC mRNA expression was noticed in laryngeal and tongue tumors of advanced TNM stage or bigger size, compared to early-stage or smaller tumors, respectively. No statistically significant differences were observed between SCCs resected from pharynx, buccal mucosa, or nasal cavity, and their normal counterparts.ConclusionThis is the first study examining the DDC mRNA expression in HNSCC. According to our results, DDC mRNA expression may constitute a potential prognostic biomarker in tongue and/or larynx SCCs, which principally represent the overwhelming majority of HNSCC cases.

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DDC (dopa decarboxylase (aromatic L-amino acid decarboxylase))

Abstract: This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.

Cited by 6 publications

References 78 publications

Emerging Role of l-Dopa Decarboxylase in Flaviviridae Virus Infections

Emerging Role of l-Dopa Decarboxylase in Flaviviridae Virus Infections

Alteration of L-Dopa decarboxylase expression in SARS-CoV-2 infection and its association with the interferon-inducible ACE2 isoform

L-DOPA decarboxylase mRNA expression is associated with tumor stage and size in head and neck squamous cell carcinoma: a retrospective cohort study

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