Structural and functional analogies and differences between histidine decarboxylase and aromatic l-amino acid decarboxylase molecular networks: Biomedical implications.

Human histidine decarboxylase (HDC) and dopa decarboxilase (DDC) are highly homologous enzymes responsible for the synthesis of biogenic amines (BA) like histamine, and serotonin and dopamine, respectively. The enzymes share many structural and functional analogies, while their product metabolisms also follow similar patterns that are confluent in some metabolic steps. They are involved in common physiological functions, such as neurotransmission, gastrointestinal track function, immunity, cell growth and cell differentiation. As a consequence, metabolic elements of both BA subfamilies are also co-participants in a long list of human diseases. This review summarizes the analogies and differences in their origin (HDC and DDC) as well as their common pathophysiological scenarios. The major gaps of information are also underlined, as they delay the possibility of holistic approaches that would help personalized medicine and pharmacological initiatives for prevalent and rare diseases.

Structural perspective on the direct inhibition mechanism of EGCG on mammalian histidine decarboxylase and DOPA decarboxylase.

Histidine decarboxylase (HDC) and l-aromatic amino acid decarboxylase (DDC) are homologous enzymes that are responsible for the synthesis of important neuroactive amines related to inflammatory, neurodegenerative, and neoplastic diseases. Epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, has been shown to target histamine-producing cells and to promote anti-inflammatory, antitumor, and antiangiogenic effects. Previous experimental work has demonstrated that EGCG has a direct inhibitory effect on both HDC and DDC. In this study, we investigated the binding modes of EGCG to HDC and DDC as a first step for designing new polyphenol-based HDC/DDC-specific inhibitors.

Targeting of histamine producing cells by EGCG: a green dart against inflammation?

No disponible

The human body is made of some 250 different cell types. From them, only a small subset of cell types is able to produce histamine. They include some neurons, enterochromaffin-like cells, gastrin-containing cells, mast cells, basophils, and monocytes/macrophages, among others. In spite of the reduced number of these histamine-producing cell types, they are involved in very different physiological processes. Their deregulation is related with many highly prevalent, as well as emergent and rare diseases, mainly those described as inflammation-dependent pathologies, including mastocytosis, basophilic leukemia, gastric ulcer, Crohn disease, and other inflammatory bowel diseases. Furthermore, oncogenic transformation switches some non-histamine-producing cells to a histamine producing phenotype. This is the case of melanoma, small cell lung carcinoma, and several types of neuroendocrine tumors. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. In fact, EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases (AU)

Targeting of histamine producing cells by EGCG: a green dart against inflammation?

The human body is made of some 250 different cell types. From them, only a small subset of cell types is able to produce histamine. They include some neurons, enterochromaffin-like cells, gastrin-containing cells, mast cells, basophils, and monocytes/macrophages, among others. In spite of the reduced number of these histamine-producing cell types, they are involved in very different physiological processes. Their deregulation is related with many highly prevalent, as well as emergent and rare diseases, mainly those described as inflammation-dependent pathologies, including mastocytosis, basophilic leukemia, gastric ulcer, Crohn disease, and other inflammatory bowel diseases. Furthermore, oncogenic transformation switches some non-histamine-producing cells to a histamine producing phenotype. This is the case of melanoma, small cell lung carcinoma, and several types of neuroendocrine tumors. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target histamine-producing cells producing great alterations in their behavior, with relevant effects on their proliferative potential, as well as their adhesion, migration, and invasion potentials. In fact, EGCG has been shown to have potent anti-inflammatory, anti-tumoral, and anti-angiogenic effects and to be a potent inhibitor of the histamine-producing enzyme, histidine decarboxylase. Herein, we review the many specific effects of EGCG on concrete molecular targets of histamine-producing cells and discuss the relevance of these data to support the potential therapeutic interest of this compound to treat inflammation-dependent diseases.

Targeting polyamines and biogenic amines by green tea epigallocatechin-3-gallate.

Biogenic amines and polyamines are organic polycations derived from aromatic or cationic amino acids. They exert pleiotropic effects, more related to intercellular communication in the case of biogenic amines, and to intracellular signaling in the case of polyamines. The bioactive compound epigallocatechin-3-gallate (EGCG), a major component of green tea, has been shown to target key enzyme of biogenic amine and polyamine metabolic pathways. Herein, we review the specific effects of EGCG on concrete molecular targets of both biogenic amine and polyamine metabolic pathways, and discuss the relevance of these data to support the potential therapeutic interest of this compound.

The polyamine and histamine metabolic interplay in cancer and chronic inflammation.

PURPOSE OF REVIEW: To provide an update on the major research contributing to deciphering the metabolic interplay of polyamines/histamine and its impact in cancer and chronic inflammation. RECENT FINDINGS: The most recent and relevant findings that might reflect a link between the polyamines/histamine metabolic interplay and the development of cancer and chronic inflammation-related diseases include: the observation that histamine catabolism is downregulated in the colonic mucosa of patients with colonic adenoma; the finding that some polyamine and histamine-related metabolites are different between a breast cancer cell line and a reference mammary epithelial cell line; and the demonstration of the critical role that mast cells (a cell type in which the polyamine/histamine metabolic interplay has been confirmed) play in the development of pancreatic tumors. There is still, however, a lack of specific studies elucidating the exact contribution of the polyamine/histamine metabolic interplay in these clinical settings. SUMMARY: In mammalian cells, a polyamine/histamine metabolic interplay has been extensively proven; however, its ultimate effect on human health largely depends on the cell type and environment. Information on this topic is currently fragmented in the literature. In order to develop efficient intervention strategies, it will be necessary to establish an integrated and holistic view of the role of the polyamine/histamine metabolic interplay in each pathological state.