Immunocytochemical Evidence Suggesting that Diamine Oxidase Catalyzes Biosynthesis of γ-Aminobutyric Acid in Antropyloric Gastrin Cells

Hardt, Jesper; Larsson, Lars‐Inge; Hougaard, David M.

doi:10.1177/002215540004800612

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…Moreover, GABA obtained from this pathway in gastrin-producing enteroendocrine cells is a postulated paracrine modulator within the gastric mucosa (44,45). These findings, together with the observations that (i) ABP1 is cell membrane-associated (46,47) and (ii) its mRNA is called ''Present'' almost exclusively in poorvs.…”

Section: Generation Of Metabolic Signatures Indicative Of Poor-prognosismentioning

confidence: 65%

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

Ippolito

Jain

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

104

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Human neuroendocrine (NE) cancers range from relatively indolent to highly aggressive. In this study, we combine functional genomics with metabolomics to identify features of NE cancers associated with a poor outcome. Analysis of GeneChip datasets of primary prostate tumors, as well as lymph node and liver metastases from transgenic mice with a NE cell cancer, plus derived NE cell lines yielded a signature of 446 genes whose expression is enriched in neoplastic mouse prostatic NE cells. This signature was used for in silico metabolic reconstructions of NE cell metabolism, directed liquid chromatography͞tandem MS analysis of metabolites in prostatic NE tumors and cell lines, and analysis of GeneChip datasets of human NE tumors with good or poor prognoses. 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 membraneassociated amine oxidase, amiloride-binding protein 1. Electrophysiological studies disclosed that imidazole-4-acetate can bind and activate GABAA receptors expressed by transformed NE cells, thus providing a previously uncharacterized paradigm for NE tumor cell signaling. Transcriptional, metabolic, and electrophysiologic features of transformed mouse NE cells are also evident in neural progenitor cells.GABA signaling ͉ MS ͉ metastatic neuroendocrine cancers ͉ polyamine metabolism ͉ transcriptome-directed metabolomics H uman neuroendocrine (NE) cancers (NECs) can arise in neuroectodermal tissues or in endoderm-derived epithelia (e.g., pheochromocytomas and small cell lung cancers, respectively). Many types of NECs are aggressive and diagnosed only after metastatic spread (1, 2). In addition, the appearance of NE features in cancers arising from cells that do not normally express neural or endocrine fates is often associated with more aggressive disease (3-5). A panel of biomarkers and mediators of tumorigenesis is needed for better diagnosis and stratification of NECs and new, more efficacious therapeutic approaches. In this report, we present one approach for addressing this issue that uses a combination of transgenic mice with a metastatic cancer arising from their prostatic NE cell lineage, NE cell lines established from this cancer, human NE tumors with varying degrees of aggressiveness, functional genomics, and MS-based metabolomics.The prostate contains three epithelial lineages: secretory, basal, and NE (6). The secretory or luminal cell is the most abundant type and requires continuous exposure to androgens for its survival (7-11). Basal cells represent the primary proliferating epithelial population and are not androgen-dependent (12, 13). NE cells are rare (Ͻ1% of the total), have distinctive projections that allow them to contact epithelial neighbors located several cell diameters away, and secrete a variety of neuropeptides and neurotransmitters (14-17). Conventional adenocarcinoma of the prostate (C...

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Section: Generation Of Metabolic Signatures Indicative Of Poor-prognosismentioning

confidence: 65%

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

Ippolito

Jain

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

104

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“…3). GABA derived from this pathway is proposed to be a paracrine signaling molecule exported by enteroendocrine cells in the gastric mucosa [114,115]. Increased ABP1 activity has been demonstrated in NE carcinomas including small cell lung carcinomas and medullary thyroid carcinoma [40,116].…”

Section: Gaba Biosynthesismentioning

confidence: 99%

Current concepts in neuroendocrine cancer metabolism

Ippolito

2006

Pituitary

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Neuroendocrine (NE) cancers occur in multiple anatomic locations and range in prognosis from indolent to aggressive. In addition, adenocarcinomas can express gene products associated with NE cells, referred to as NE differentiation (NED), which correlates with poor prognosis and aggressive disease. Several metabolites and peptides produced by NE cells have been discovered that engage in cellular signaling and have autocrine and paracrine effects on cancer cell proliferation. This review focuses on the current knowledge of small molecule metabolism in NE cancers involving the synthesis of biogenic amine, polyamine, and amino acid neurotransmitters. Systems biology-directed approaches to NE cancer metabolism using gene expression profiling, liquid chromatography/mass spectrometry (LC/MS) and nuclear magnetic resonance (NMR) are also discussed. Furthermore, knowledge of metabolic and signaling pathways in NE cancers has led to the successful implementation of therapeutic regimens in cell culture and animal models of NE carcinogenesis.

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“…GAD catalyzes l -glutamic acid to GABA and carbon dioxide through an irreversible α-decarboxylation reaction. GAD is a calcium/calmodulin-dependent enzyme in GABA synthesis. − Another GABA synthesis pathway is related to polyamine degradation, in which diamine oxidase (DAO; EC 1.4.3.6) is the rate-limiting enzyme for GABA synthesis. − …”

Section: Introductionmentioning

confidence: 99%

Influence of Light on the Free Amino Acid Content and γ-Aminobutyric Acid Synthesis in Brassica juncea Seedlings

Li¹,

Kim²,

Uddin³

et al. 2013

J. Agric. Food Chem.

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Glutamate decarboxylase (GAD; EC 4.1.1.15) is an important enzyme in γ-aminobutyric acid (GABA) biosynthesis. Here we report the influence of light on amino acid accumulation and investigate the molecular mechanism by which light influences GABA biosynthesis at the seedling stage of two mustard (Brassica juncea) cultivars (green-leaf and purple-leaf). Gene expression profiles of four GAD-encoding genes (GAD1, GAD2, GAD4a, and GAD4b) and their impact on GABA biosynthesis were analyzed. Light exerted an obvious influence on amino acid accumulation in mustard seedlings. GAD gene expression was also significantly regulated by light/dark or dark treatment, which differentially regulated GABA biosynthesis in B. juncea seedlings. High-performance liquid chromatography (HPLC) revealed that the seeds of purple cultivars contain a higher amount of free amino acids and GABA than do the seeds of green cultivars. After seed germination, however, the accumulation of free amino acids peaked in dark-treated seedlings on day 9 in both cultivars, whereas GABA synthesis peaked at 9 days under light conditions. This study may provide a foundation for understanding the effect of light on amino acids, particularly GABA biosynthesis in Brassica plants.

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Immunocytochemical Evidence Suggesting that Diamine Oxidase Catalyzes Biosynthesis of γ-Aminobutyric Acid in Antropyloric Gastrin Cells

Cited by 10 publications

References 33 publications

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

An integrated functional genomics and metabolomics approach for defining poor prognosis in human neuroendocrine cancers

Current concepts in neuroendocrine cancer metabolism

Influence of Light on the Free Amino Acid Content and γ-Aminobutyric Acid Synthesis in Brassica juncea Seedlings

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