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Hiroshi Ohtsu - One of the best experts on this subject based on the ideXlab platform.

  • changes in Histidine Decarboxylase expression influence extramedullary hematopoiesis in postnatal mice
    Anatomical Record-advances in Integrative Anatomy and Evolutionary Biology, 2021
    Co-Authors: Hirotada Otsuka, Hiroshi Ohtsu, Yasuo Endo, Satoshi Inoue, Mutsuki Kuraoka, Miki Koh, Hideki Yagi, Masanori Nakamura, Satoshi Soeta
    Abstract:

    Histidine Decarboxylase (HDC), histamine synthase, is expressed in hematopoietic stem cells and in lineage-committed progenitors in the bone marrow (BM). However, the role of histamine in hematopoiesis is not well described. To evaluate the role of histamine in hematopoiesis, we analyzed the changes in HDC expression at hematopoietic sites, the BM, spleen, and liver of 2-, 3-, and 6-week-old wild-type mice. We also performed morphological analyses of the hematopoietic sites using HDC-deficient (HDC-KO) mice. In wild-type adults, HDC expression in the BM was higher than that in the spleen and liver and showed an age-dependent increase. Histological analysis showed no significant change in the adult BM and spleen of HDC-KO mice compared to wild-type mice. In the liver, HDC expression was temporarily increased at 3 weeks and decreased at 6 weeks of age. Morphological analysis of the liver revealed more numerous hematopoietic colonies and megakaryocytes in HDC-KO mice compared to wild-type mice at 2 and 3 weeks of age, whereas no changes were observed in adults. Most of these hematopoietic colonies consisted of B220-positive B-lymphocytes and TER119-positive erythroblasts and were positive for the cell proliferation marker PCNA. Notably, these hematopoietic colonies declined in HDC-KO mice upon N-acetyl histamine treatment. A significant increase in the expression of hematopoiesis-related cytokines, Il3, Il7, Epo, Gcsf, and Cxcl12 mRNA was observed in the liver of 3-week-old HDC-KO mice compared to wild-type mice. These results suggest that histamine-deficiency may maintain an microenvironment suitable for hematopoiesis by regulating hematopoiesis-related cytokine expression in the liver of postnatal mice.

  • Histidine Decarboxylase deficiency inhibits NBP-induced extramedullary hematopoiesis by modifying bone marrow and spleen microenvironments
    International Journal of Hematology, 2021
    Co-Authors: Hirotada Otsuka, Hiroshi Ohtsu, Yasuo Endo, Satoshi Inoue, Masanori Nakamura, Syunya Noguchi, Satoshi Soeta
    Abstract:

    Histidine Decarboxylase (HDC), a histamine synthase, is expressed in various hematopoietic cells and is induced by hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF). We previously showed that nitrogen-containing bisphosphonate (NBP)-treatment induces extramedullary hematopoiesis via G-CSF stimulation. However, the function of HDC in NBP-induced medullary and extramedullary hematopoiesis remains unclear. Here, we investigated changes in hematopoiesis in wild-type and HDC-deficient (HDC-KO) mice. NBP treatment did not induce anemia in wild-type or HDC-KO mice, but did produce a gradual increase in serum G-CSF levels in wild-type mice. NBP treatment also enhanced Hdc mRNA expression and erythropoiesis in the spleen and reduced erythropoiesis in bone marrow and the number of vascular adhesion molecule 1 (VCAM-1)-positive macrophages in wild-type mice, as well as increased the levels of hematopoietic progenitor cells and proliferating cells in the spleen and enhanced expression of bone morphogenetic protein 4 ( Bmp4 ), CXC chemokine ligand 12 ( Cxcl12 ), and hypoxia inducible factor 1 ( Hif1 ) in the spleen. However, such changes were not observed in HDC-KO mice. These results suggest that histamine may affect hematopoietic microenvironments of the bone marrow and spleen by changing hematopoiesis-related factors in NBP-induced extramedullary hematopoiesis.

  • lipopolysaccharide induced expansion of Histidine Decarboxylase expressing ly6g myeloid cells identified by exploiting Histidine Decarboxylase bac gfp transgenic mice
    Scientific Reports, 2019
    Co-Authors: Jun Takai, Hiroshi Ohtsu, Atsushi Sato, Satoshi Uemura, Tsutomu Fujimura, Masayuki Yamamoto, Takashi Moriguchi
    Abstract:

    Histamine is a biogenic amine that is chiefly produced in mast cells and basophils and elicits an allergic response upon stimulation. Histidine Decarboxylase (HDC) is a unique enzyme that catalyzes the synthesis of histamine. Therefore, the spatiotemporally specific Hdc gene expression profile could represent the localization of histamine-producing cells under various pathophysiological conditions. Although the bioactivity of histamine is well defined, the regulatory mechanism of Hdc gene expression and the distribution of histamine-producing cell populations in various disease contexts remains unexplored. To address these issues, we generated a Histidine Decarboxylase BAC (bacterial artificial chromosome) DNA-directed GFP reporter transgenic mouse employing a 293-kb BAC clone containing the entire Hdc gene locus and extended flanking sequences (Hdc-GFP). We found that the GFP expression pattern in the Hdc-GFP mice faithfully recapitulated that of conventional histamine-producing cells and that the GFP expression level mirrored the increased Hdc expression in lipopolysaccharide (LPS)-induced septic lungs. Notably, a CD11b+Ly6G+Ly6Clow myeloid cell population accumulated in the lung during sepsis, and most of these cells expressed high levels of GFP and indeed contain histamine. This study reveals the accumulation of a histamine-producing myeloid cell population during sepsis, which likely participates in the immune process of sepsis.

  • Histidine Decarboxylase knockout mice a genetic model of tourette syndrome show repetitive grooming after induced fear
    Neuroscience Letters, 2015
    Co-Authors: Hiroshi Ohtsu, Christopher Pittenger
    Abstract:

    Abstract Tics, such as are seen in Tourette syndrome (TS), are common and can cause profound morbidity, but they are poorly understood. Tics are potentiated by psychostimulants, stress, and sleep deprivation. Mutations in the gene Histidine Decarboxylase (Hdc) have been implicated as a rare genetic cause of TS, and Hdc knockout mice have been validated as a genetic model that recapitulates phenomenological and pathophysiological aspects of the disorder. Tic-like stereotypies in this model have not been observed at baseline but emerge after acute challenge with the psychostimulant d -amphetamine. We tested the ability of an acute stressor to stimulate stereotypies in this model, using tone fear conditioning. Hdc knockout mice acquired conditioned fear normally, as manifested by freezing during the presentation of a tone 48 h after it had been paired with a shock. During the 30 min following tone presentation, knockout mice showed increased grooming. Heterozygotes exhibited normal freezing and intermediate grooming. These data validate a new paradigm for the examination of tic-like stereotypies in animals without pharmacological challenge and enhance the face validity of the Hdc knockout mouse as a pathophysiologically grounded model of tic disorders.

  • pathophysiologic role of histamine evidence clarified by Histidine Decarboxylase gene knockout mice
    International Archives of Allergy and Immunology, 2012
    Co-Authors: Hiroshi Ohtsu
    Abstract:

    The role of histamine in various murine disease models has been clarified using Histidine Decarboxylase gene knockout mice. The mice were generated using conventional gene-targeting methods. Studies, including ours, using knockout mice have shown that the activity of histamine is not limited to allergic, peptic and neurologic functions as in the old paradigm, but extends to other processes related to wound healing, circulatory disease, immunology, oncology and infectious disease. The recent observation of the activity of newly cloned histamine receptors and a pathophysiologic effect of histamine has dramatically expanded our understanding of the scope of histamine function.

Takehiko Watanabe - One of the best experts on this subject based on the ideXlab platform.

  • new functions of histamine found in Histidine Decarboxylase gene knockout mice
    Biochemical and Biophysical Research Communications, 2003
    Co-Authors: Hiroshi Ohtsu, Takehiko Watanabe
    Abstract:

    Gene targeting techniques have revolutionized the investigation of the effects of bioactive substances in pathological and physiological conditions. Histamine synthesis is uniquely catalyzed by L-Histidine Decarboxylase. The knockout mice of this gene express no histamine-producing activity and lack histamine. These mice have been used to examine the mechanisms of histamine in several known phenotypes, e.g., gastric acid secretion, contraction of smooth muscles, vascular permeability, and awakening, and have also been used to explore unreported effects of histamine in the whole body. First, we will review the former mechanisms and then move to the latter, new effects. Especially, in the latter mechanisms, we focus on several important roles of histamine in angiogenesis, neutrophil and eosinophil recruitment, bacterial infection, and systemic anaphylaxis in this review. Moreover, to our surprise, the morphology of mast cells in the knockout mice was severely affected by the absence of histamine in terms of their granules.

  • chemical kindling induced by pentylenetetrazol in histamine h1 receptor gene knockout mice h1ko Histidine Decarboxylase deficient mice hdc and mast cell deficient w wv mice
    Brain Research, 2003
    Co-Authors: Zhengyan Li, Jalal Izadi Mobarakeh, Kazuie Iinuma, Eiko Sakurai, Takehiko Watanabe, Hiroshi Ohtsu, Takeshi Watanabe, Zhong Chen, Kazuhiko Yanai
    Abstract:

    Abstract The role of brain histamine on seizure development of pentylenetetrazol (PTZ)-induced kindling was examined in H1-receptor gene knockout (H1KO), Histidine Decarboxylase-deficient (HDC−/−) and mast cell-deficient (W/Wv) mice. All H1KO, HDC−/− and W/Wv mice had accelerated seizure development of PTZ-induced kindling when compared to their respective wild-type mice. The daily PTZ-kindling increased histamine content in the cortex and diencephalon of H1KO mice, whereas the histamine content in the diencephalon of W/Wv mice was decreased. The present study indicates that histamine plays a suppressive role in seizure development through H1-receptors.

  • disruption of l Histidine Decarboxylase reduces airway eosinophilia but not hyperresponsiveness
    American Journal of Respiratory and Critical Care Medicine, 2003
    Co-Authors: Akira Koarai, Eiko Sakurai, Takehiko Watanabe, Yoko Makabekobayashi, Masakazu Ichinose, Satsuki Ishigakisuzuki, Shunsuke Yamagata, Hisatoshi Sugiura, Atsuo Kuramasu, Kunio Shirato
    Abstract:

    Histamine has a variety of airway actions and is considered to be an important mediator in asthma. This study examined the role of endogenous histamine in allergic airway eosinophil recruitment and hyperresponsiveness using L-Histidine Decarboxylase gene knockout mice. Histamine levels of the airways in L-Histidine Decarboxylase knockout mice were largely diminished compared with wild-type mice. Inhalation challenge with ovalbumin (OVA) in OVA-sensitized wild-type mice caused eosinophil accumulation in the lung as well as airway hyperresponsiveness to methacholine 3 days after the challenge. The eosinophil recruitment was significantly reduced in the knockout mice. In the bone marrow, the proliferation of eosinophils was enhanced after OVA challenge in the wild-type mice; however, the proliferation was significantly reduced in the knockout mice. The induction of P-selectin in the lung after OVA challenge was also inhibited in the knockout mice. In contrast, airway hyperresponsiveness was not suppressed in the knockout mice. These results suggest that endogenous histamine is involved in the accumulation of eosinophils into the airways after allergic challenge, possibly acting in the bone marrow and producing P-selectin in the airways. Furthermore, allergen-induced airway hyperresponsiveness appeared to occur independently of airway eosinophilia in our present model.

  • enhancement of neutrophil infiltration in Histidine Decarboxylase deficient mice
    Immunology, 2002
    Co-Authors: Noriyasu Hirasawa, Takehiko Watanabe, Hiroshi Ohtsu, Kazuo Ohuchi
    Abstract:

    The roles of histamine in the anaphylactic increase in vascular permeability and leucocyte infiltration were analysed in an air pouch-type allergic inflammation model in Histidine Decarboxylase-deficient (HDC - / - ) miceand wild-type mice. In the immunized wild-type mice, histamine content in the pouch fluid and vascular permeability in the anaphylaxis phase were increased by injection of the antigen solution into the air pouch. However, in the immunized HDC - / - mice, the antigen challenge did not increase histamine content in the pouch fluid and vascular permeability in the anaphylaxis phase. Number of leucocytes (more than 83% are neutrophils) in the pouch fluid 4-24 hr after the antigen challenge in the HDC - / - mice was significantly higher than that in the wild-type mice. Simultaneous injection of histamine with the antigen solution into the air pouch of the immunized HDC - / - mice reduced the antigen-induced leucocyte infiltration at 4 hr. Simultaneous injection of the H2 antagonist cimetidine but not the H1 antagonist pyrilamine with the antigen solution into the air pouch of the immunized wild-type mice further increased leucocyte infiltration at 4 hr. The levels of macrophage inflammatory protein-2 at 2 hr and of tumour necrosis factor-α at 4 hr in the pouch fluid of the HDC - / - mice were significantly higher than those of the wild-type mice. These findings indicate that histamine plays significant roles not only in the anaphylactic increase in vascular permeability via H1 receptors but also in the negative regulation of neutrophil infiltration via H2 receptors in allergic inflammation.

  • defective angiogenesis in the inflammatory granulation tissue in Histidine Decarboxylase deficient mice but not in mast cell deficient mice
    Journal of Experimental Medicine, 2002
    Co-Authors: Ajoy Kuma Ghosh, Noriyasu Hirasawa, Takehiko Watanabe, Hiroshi Ohtsu, Kazuo Ohuchi
    Abstract:

    We have analyzed the role of histamine in the angiogenesis of the granulation tissue in Histidine Decarboxylase–deficient (HDC−/−) mice, mast cell–deficient mice (WBB6F1-W/WV), and their corresponding wild-type mice (HDC+/+ and WBB6F1+/+). In HDC+/+ mice, subcutaneous implantation of a cotton thread in the dorsum induced granulation tissue formation with angiogenesis, while the topical injection of antivascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC−/− mice which showed lower VEGF levels in the granulation tissue, there was notably less angiogenesis and granulation tissue formation than in HDC+/+ mice. The topical injection of histamine or the H2 agonist dimaprit rescued the defective angiogenesis and granulation tissue formation in HDC−/− mice. There was no significant difference in the granulation tissue formation and angiogenesis between WBB6F1-W/WV and WBB6F1+/+ mice. In addition, macrophages in the granulation tissue were found to express HDC. Our findings indicate that histamine derived from nonmast cells plays a significant role in the angiogenesis of the inflammatory granulation tissue.

Zhong Chen - One of the best experts on this subject based on the ideXlab platform.

  • carnosine protects against permanent cerebral ischemia in Histidine Decarboxylase knockout mice by reducing glutamate excitotoxicity
    Free Radical Biology and Medicine, 2010
    Co-Authors: Yao Shen, Hiroshi Ohtsu, Yanying Fan, Jianxiang Zhang, Haijing Yan, Zhong Chen
    Abstract:

    Abstract Recently, we showed that carnosine protects against NMDA-induced excitotoxicity in differentiated PC12 cells through a histaminergic pathway. However, whether the protective effect of the carnosine metabolic pathway also occurs in ischemic brain is unknown. Utilizing the model of permanent middle cerebral artery occlusion (pMCAO) in mice, we found that carnosine significantly improved neurological function and decreased infarct size in both Histidine Decarboxylase knockout and the corresponding wild-type mice to the same extent. Carnosine decreased the glutamate levels and preserved the expression of glutamate transporter-1 (GLT-1) but not the glutamate/aspartate transporter in astrocytes exposed to ischemia in vivo and in vitro. It suppressed the dissipation of ΔΨ m and generation of mitochondrial reactive oxygen species (ROS) induced by oxygen–glucose deprivation in astrocytes. Furthermore, carnosine also decreased the mitochondrial ROS and reversed the decrease in GLT-1 induced by rotenone. These findings are the first to demonstrate that the mechanism of carnosine action in pMCAO may not be mediated by the histaminergic pathway, but by reducing glutamate excitotoxicity through the effective regulation of the expression of GLT-1 in astrocytes due to improved mitochondrial function. Thus, our study reveals a novel antiexcitotoxic agent in ischemic injury.

  • carnosine protects against permanent cerebral ischemia in Histidine Decarboxylase knockout mice by reducing glutamate excitotoxicity
    Free Radical Biology and Medicine, 2010
    Co-Authors: Yao Shen, Hiroshi Ohtsu, Yanying Fan, Jianxiang Zhang, Haijing Yan, Zhong Chen
    Abstract:

    Recently, we showed that carnosine protects against NMDA-induced excitotoxicity in differentiated PC12 cells through a histaminergic pathway. However, whether the protective effect of the carnosine metabolic pathway also occurs in ischemic brain is unknown. Utilizing the model of permanent middle cerebral artery occlusion (pMCAO) in mice, we found that carnosine significantly improved neurological function and decreased infarct size in both Histidine Decarboxylase knockout and the corresponding wild-type mice to the same extent. Carnosine decreased the glutamate levels and preserved the expression of glutamate transporter-1 (GLT-1) but not the glutamate/aspartate transporter in astrocytes exposed to ischemia in vivo and in vitro. It suppressed the dissipation of Delta Psi(m) and generation of mitochondrial reactive oxygen species (ROS) induced by oxygen-glucose deprivation in astrocytes. Furthermore, carnosine also decreased the mitochondrial ROS and reversed the decrease in GLT-1 induced by rotenone. These findings are the first to demonstrate that the mechanism of carnosine action in pMCAO may not be mediated by the histaminergic pathway, but by reducing glutamate excitotoxicity through the effective regulation of the expression of GLT-1 in astrocytes due to improved mitochondrial function. Thus, our study reveals a novel antiexcitotoxic agent in ischemic injury.

  • morphine induces conditioned place preference behavior in Histidine Decarboxylase knockout mice
    Neuroscience Letters, 2010
    Co-Authors: Yingxia Gong, Weiping Zhang, Wenting Shou, Kai Zhong, Zhong Chen
    Abstract:

    Abstract Pharmacological and lesion studies have shown that histamine exerts inhibitory effects on morphine-induced reward-seeking behavior. The present study was designed to further investigate the involvement of endogenous histamine in morphine-induced reward-seeking behavior using Histidine Decarboxylase gene knockout (HDC-KO) mice. Conditioned place preference (CPP) was present in both wild-type (WT) and HDC-KO mice treated with 5 or 10 mg/kg morphine. HDC-KO mice showed stronger morphine-induced CPP as compared with WT mice. Meanwhile, morphine significantly increased dopamine level in the VTA and NAc, especially in HDC-KO mice. However, the extinction of CPP is similar between WT and HDC-KO mice. Moreover, naloxone-precipitated withdrawal jumping was markedly decreased in HDC-KO mice. These results indicate that endogenous histamine inhibits the development, but not the extinction, of morphine-induced CPP and reduces morphine withdrawal sign, probably through modulating dopaminergic activity in the brain.

  • carnosine inhibits pentylenetetrazol induced seizures by histaminergic mechanisms in Histidine Decarboxylase knock out mice
    Neuroscience Letters, 2007
    Co-Authors: Zhengbing Zhuge, Hiroshi Ohtsu, Dengchang Wu, Shuang Wang, Zhong Chen
    Abstract:

    Abstract In the present study, we used both Histidine Decarboxylase-deficient (HDC-KO) mice and wild-type (WT) mice to elucidate the possible role of carnosine in pentylenetetrazol (PTZ)-induced seizures. In the acute PTZ challenge study, PTZ (75 mg/kg) was injected intraperitoneally (i.p.) to induce seizures. Carnosine (200, 500 or 1000 mg/kg, i.p.) significantly decreased seizure stage, and prolonged the latency for myoclonic jerks in WT mice in a dose-dependent manner. The effects of carnosine (500 mg/kg) were time-dependent and reached a peak at 1 h. However, it had no significant effect on HDC-KO mice. Carnosine (500 mg/kg) also significantly elevated the thresholds in WT mice but not HDC-KO mice following intravenous (tail vein) administration of PTZ. We also found that α-fluoromethylHistidine substantially reversed the protective effects of carnosine in WT mice. In addition, carnosine pretreatment reduced the cortical EEG activity induced by PTZ (75 mg/kg, i.p.). These results indicate that carnosine can protect against PTZ-induced seizures and its action is mainly through the carnosine–Histidine–histamine metabolic pathway. This suggests that carnosine may be an endogenous anticonvulsant factor in the brain and may be used as a new antiepileptic drug in the future.

  • chemical kindling induced by pentylenetetrazol in histamine h1 receptor gene knockout mice h1ko Histidine Decarboxylase deficient mice hdc and mast cell deficient w wv mice
    Brain Research, 2003
    Co-Authors: Zhengyan Li, Jalal Izadi Mobarakeh, Kazuie Iinuma, Eiko Sakurai, Takehiko Watanabe, Hiroshi Ohtsu, Takeshi Watanabe, Zhong Chen, Kazuhiko Yanai
    Abstract:

    Abstract The role of brain histamine on seizure development of pentylenetetrazol (PTZ)-induced kindling was examined in H1-receptor gene knockout (H1KO), Histidine Decarboxylase-deficient (HDC−/−) and mast cell-deficient (W/Wv) mice. All H1KO, HDC−/− and W/Wv mice had accelerated seizure development of PTZ-induced kindling when compared to their respective wild-type mice. The daily PTZ-kindling increased histamine content in the cortex and diencephalon of H1KO mice, whereas the histamine content in the diencephalon of W/Wv mice was decreased. The present study indicates that histamine plays a suppressive role in seizure development through H1-receptors.

Hiroshi Ueno - One of the best experts on this subject based on the ideXlab platform.

  • The ellagitannin trimer rugosin G inhibits recombinant human Histidine Decarboxylase
    2019
    Co-Authors: Yoko Nitta, Motoyoshi Sakaue, Hirohumi Komori, Hiroshi Ueno, Hideyuki Ito, Daiki Takeshima, Mikiko Ito, Hiroe Kikuzaki
    Abstract:

    Rugosin G, an ellagitannin trimer, was isolated from the water-soluble fraction of red rose petals, and its inhibitory activity against recombinant human Histidine Decarboxylase was investigated. Rugosin G showed potent inhibition compared to ellagitannin monomers and a dimer with macrocyclic structure (oenothein B), suggesting the potent inhibition of rugosin G was attributed to its linear oligomeric conformation. Abbreviations: HDC, Histidine Decarboxylase; Me2CO, acetone; EtOAc, ethyl acetate

  • Inhibition of Morganella morganii Histidine Decarboxylase Activity and Histamine Accumulation in Mackerel Muscle Derived from Filipendula ulumaria Extracts
    Journal of food protection, 2016
    Co-Authors: Yoko Nitta, Hiroe Kikuzaki, Motoyoshi Sakaue, Mikiko Ito, Fumiko Yasukata, Noritoshi Kitamoto, Hiroshi Ueno
    Abstract:

    Filipendula ulmaria, also known as meadowsweet, is an herb; its extract was examined for the prevention of histamine production, primarily that caused by contaminated fish. The efficacy of meadowsweet was assessed using two parameters: inhibition of Morganella morganii Histidine Decarboxylase (HDC) and inhibition of histamine accumulation in mackerel. Ellagitannins from F. ulmaria (rugosin D, rugosin A methyl ester, tellimagrandin II, and rugosin A) were previously shown to be potent inhibitors of human HDC; and in the present work, these compounds inhibited M. morganii HDC, with half maximal inhibitory concentration values of 1.5, 4.4, 6.1, and 6.8 μM, respectively. Application of the extracts (at 2 wt%) to mackerel meat yielded significantly decreased histamine accumulation compared with treatment with phosphate-buffered saline as a control. Hence, F. ulmaria exhibits inhibitory activity against bacterial HDC and might be effective for preventing food poisoning caused by histamine.

  • Inhibitory activity of Filipendula ulmaria constituents on recombinant human Histidine Decarboxylase.
    Food chemistry, 2012
    Co-Authors: Yoko Nitta, Hiroe Kikuzaki, Toshiaki Azuma, Motoyoshi Sakaue, Yoshiki Higuchi, Hirohumi Komori, Hiroshi Ueno
    Abstract:

    Histidine Decarboxylase (HDC) catalyses the formation of histamine, a bioactive amine. Agents that control HDC activity are beneficial for treating histamine-mediated symptoms, such as allergies and stomach ulceration. We searched for inhibitors of HDC from the ethyl acetate extract of the petal of Filipendula ulmaria, also called meadowsweet. Rugosin D, rugosin A, rugosin A methyl ester (a novel compound), and tellimagrandin II were the main components; these 4 ellagitannins exhibited a non-competitive type of inhibition, with K(i) values of approximately 0.35-1 μM. These K(i) values are nearly equal to that of Histidine methyl ester (K(i)=0.46 μM), an existing substrate analogue inhibitor. Our results show that food products contain potent HDC inhibitors and that these active food constituents might be useful for designing clinically available HDC inhibitors.

  • structural study reveals that ser 354 determines substrate specificity on human Histidine Decarboxylase
    Journal of Biological Chemistry, 2012
    Co-Authors: Hirofumi Komori, Yoko Nitta, Hiroshi Ueno, Yoshiki Higuchi
    Abstract:

    Histamine is an important chemical mediator for a wide variety of physiological reactions. l-Histidine Decarboxylase (HDC) is the primary enzyme responsible for histamine synthesis and produces histamine from Histidine in a one-step reaction. In this study, we determined the crystal structure of human HDC (hHDC) complexed with the inhibitor Histidine methyl ester. This structure shows the detailed features of the pyridoxal-5′-phosphate inhibitor adduct (external aldimine) at the active site of HDC. Moreover, a comparison of the structures of hHDC and aromatic l-amino acid (l-DOPA) Decarboxylase showed that Ser-354 was a key residue for substrate specificity. The S354G mutation at the active site enlarged the size of the hHDC substrate-binding pocket and resulted in a decreased affinity for Histidine, but an acquired ability to bind and act on l-DOPA as a substrate. These data provide insight into the molecular basis of substrate recognition among the group II pyridoxal-5′-phosphate-dependent Decarboxylases.

  • food components inhibiting recombinant human Histidine Decarboxylase activity
    Journal of Agricultural and Food Chemistry, 2007
    Co-Authors: Yoko Nitta, Hiroe Kikuzaki, Hiroshi Ueno
    Abstract:

    Histidine Decarboxylase (HDC) catalyzes histamine formation from Histidine. Histamine is a bioactive amine acting as a neurotransmitter as well as a chemical mediator. Phenolic food components have been tested for their ability to inhibit recombinant human HDC. Epicatechin gallate (ECG) was found to be a potent inhibitor as it inhibited HDC activity in a competitive manner with Ki = 10 μM against l-Histidine. Epigallocatechin gallate (EGCG) showed time-dependent inhibition which disappeared under anaerobic conditions. It is probable that time-dependent inhibition could be due to the result of autoxidation of EGCG. The initial burst observed for EGCG suggests that EGCG itself is involved in HDC inhibition as observed for ECG. Our present results have shown that the tested food components can inhibit HDC activity. This inhibition likely affects histamine biosynthesis and possibly leads to controlling the biological action induced by histamine. Therefore, those food components exhibiting HDC inhibitory activ...

Andras Falus - One of the best experts on this subject based on the ideXlab platform.

  • extramedullary hematopoiesis is dysregulated in histamine free Histidine Decarboxylase knockout hdc mice
    Inflammation Research, 2010
    Co-Authors: Zsuzsanna Horvath, Andras Falus, Eva Pallinger, Győző Horvath, Ivett Jelinek, Gizella Veszely, Jozsef Fűresz, Edit I Buzas
    Abstract:

    In this study we investigated the role of histamine on the extramedullary hematopoiesis. Male Histidine Decarboxylase knockout (HDC−/−) mice and wild-type mice were used (n = 5/group). Groups of mice received sublethal total-body gamma irradiation at a single dose of 4 Gy. Spleen cells were studied at different time points post-irradiation by flow cytometry, colony forming unit (CFU) assay, and real-time PCR. For statistical analysis Student’s t test, ANOVA, and Holm-Sidak post-hoc test were used. By day 14 after irradiation, spleen cell counts increased almost eightfold in wild-type and not even fourfold in HDC−/− mice (P < 0.01). The proliferative capacity and interleukin-3 signaling of stem cells were impaired in HDC−/− mice. STAT5 mRNA expression was decreased in granulocyte-myeloid colonies by 72.9 ± 8.6% (P < 0.001), compared to the wild-type. The absence of histamine adversely affects splenic hematopoiesis via direct and indirect mechanisms.

  • highly activated c fos expression in specific brain regions ependyma circumventricular organs choroid plexus of Histidine Decarboxylase deficient mice in response to formalin induced acute pain
    Neuropharmacology, 2007
    Co-Authors: Miklos Palkovits, Edit I Buzas, Maria A Deli, Katalin Gallatz, Zsuzsanna Toth, Andras Falus
    Abstract:

    Activation of different brain regions for acute pain-related stress induced by a single subcutaneous injection of 4% formalin was investigated in Histidine Decarboxylase-deficient mice. Besides pain- and stress-related brain areas and the tuberomamillary neurons, strong Fos activation and c-fos mRNA expression were found in distinct brain regions and cell types, which have not been activated in wild type control mice. These structures include the circumventricular organs (organum vasculosum of the lamina terminalis, subfornical organ, area postrema), some of the ependymal cells along the wall of the ventricles, tanycytes in the third ventricle's ependyma and the median eminence, as well as in the epithelial cells of the choroid plexus in the lateral, third and fourth ventricles. All of these areas and cell types are known as compartments of the brain-blood-cerebrospinal fluid interface. The present observations provide strong evidence that an acute stressor, formalin-evoked painful stimulus elicits rapid alterations in the activity of neuroglial elements of Histidine Decarboxylase-deficient mice that are directly involved in the communication between the brain and the cerebrospinal fluid space.

  • gastric acid secretion in l Histidine Decarboxylase deficient mice
    Gastroenterology, 2002
    Co-Authors: Satoshi Tanaka, Takehiko Watanabe, Andras Falus, Kiyomi Hamada, Noboru Yamada, Yuko Sugita, Shunsuke Tonai, Bela Hunyady, Miklos Palkovits, Susumu Okabe
    Abstract:

    Abstract Background & Aims: Histamine, gastrin, and acetylcholine are known to be the primary secretagogues of gastric acid secretion, but how the roles are shared among these secretagogues remains to be fully clarified. To evaluate the cooperation between histamine and the other secretagogues, acid secretion responses induced by each secretagogue were measured in L-Histidine Decarboxylase (HDC)–deficient mice. Methods: Acid secretion was measured by the titration of acid under anesthesia. The expression of selected genes involved in acid secretion was determined by Northern blot and/or immunoblot analysis. Histamine-2 (H 2 ) receptor binding in the gastric mucosa was investigated using [ 3 H]tiotidine. Results: HDC-deficient mice showed low basal and high exogenous histamine-stimulated acid secretion. The mutant mice showed hypergastrinemia and did not undergo acid secretion upon treatment with exogenous gastrin. However, carbachol stimulated weak and transient acid secretion in the mutants. The Bmax values for H 2 and the expression of Gsα in gastric mucosal membranes were higher in the mutants than in the wild-type mice. Conclusions: This study confirms the concept that histamine production is essential for gastric acid secretion induced by gastrin, but not for that induced by carbachol. HDC-deficient mice should be a suitable model for further functional analyses of the correlation between histamine and the other acid secretagogues. GASTROENTEROLOGY 2002;122:145-155

  • suppression of melanoma cell proliferation by Histidine Decarboxylase specific antisense oligonucleotides
    Journal of Investigative Dermatology, 2001
    Co-Authors: Hargita Hegyesi, Sarolta Karpati, Valeria Laszlo, Beata Somlai, Valeria Lia Varga, Gyorgy Toth, P Kovacs, Eszter Molnar, Elena Rivera, Andras Falus
    Abstract:

    Histidine Decarboxylase (HDC) is expressed by the cells of melanoma, in which the histamine content tends to be relatively high. This study shows that elevated expression of HDC was found by western blot analysis of primary and metastatic melanoma tissue using a polyclonal HDC specific antibody. The specificity of anti-HDC antibody was confirmed by inhibition of HDC translation (i.e., immunopositivity) in melanoma cells by HDC-specific antisense oligonucleotide. Moreover, the decrease in proliferation caused by HDC antisense oligonucleotides indicates considerable functional relevance of histamine synthesis in melanoma growth and suggests a possible in situ application of specific antisense oligonucleotides for HDC in melanoma therapy.