l-Histidine decarboxylase decreases its own transcription through downregulation of ERK activity

2001 ◽  
Vol 281 (4) ◽  
pp. G1081-G1091 ◽  
Author(s):  
Rocchina Colucci ◽  
John V. Fleming ◽  
Ramnik Xavier ◽  
Timothy C. Wang
Keyword(s):  
Histidine Decarboxylase ◽  
Histamine Receptor ◽  
Inhibitory Effect ◽  
Protein Levels ◽  
Amino Terminal ◽  
Histamine Production ◽  
Extracellular Signal ◽  
Dose Dependent Fashion ◽  
Erk Activity ◽  
Dose Dependent

A poorly defined negative feedback loop decreases transcription of thel-histidine decarboxylase (HDC) gene. To help understand this regulation, we have studied the effect of HDC protein expression on HDC gene transcription in transfected AGS-B cells. Expression of the rat HDC protein inhibited HDC promoter activity in a dose-dependent fashion. The region of the HDC promoter mediating this inhibitory effect corresponded to a previously defined gastrin and extracellular signal-related kinase (ERK)-1 response element. Overexpression of the HDC protein reduced nuclear factor binding in this region. Experiments employing specific histamine receptor agonists indicated that the inhibitory effect was not dependent on histamine production, and studies with the HDC inhibitor α-fluoromethylhistidine revealed that inhibition was unrelated to enzyme activity. Instead, an enzymatically inactive region at the amino terminal of the HDC enzyme (residues 1–271) was shown to mediate inhibition. Fluorescent chimeras containing this domain were not targeted to the nucleus, arguing against specific inhibition of the HDC transcription machinery. Instead, we found that overexpression of HDC protein decreased ERK protein levels and ERK activity and that the inhibitory effect of HDC protein could be overcome by overexpression of ERK1. These data suggest a novel feedback-inhibitory role for amino terminal sequences of the HDC protein.

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

2012 ◽  
Vol 302 (3) ◽  
pp. R340-R351 ◽  
Author(s):  
Catarina Soares Potes ◽  
Christina Neuner Boyle ◽  
Peter John Wookey ◽  
Thomas Riediger ◽  
Thomas Alexander Lutz
Keyword(s):  
Area Postrema ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Neuronal Responses ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Anorectic Effect ◽  
Feeding Trials ◽  
Dose Dependent

Peripheral amylin inhibits eating via the area postrema (AP). Because amylin activates the extracellular-signal regulated kinase 1/2 (ERK) pathway in some tissues, and because ERK1/2 phosphorylation (pERK) leads to acute neuronal responses, we postulated that it may be involved in amylin's eating inhibitory effect. Amylin-induced ERK phosphorylation (pERK) was investigated by immunohistochemistry in brain sections containing the AP. pERK-positive AP neurons were double-stained for the calcitonin 1a/b receptor, which is part of the functional amylin-receptor. AP sections were also phenotyped using dopamine-β-hydroxylase (DBH) as a marker of noradrenergic neurons. The effect of fourth ventricular administration of the ERK cascade blocker U0126 on amylin's eating inhibitory action was tested in feeding trials. The number of pERK-positive neurons in the AP was highest ∼10–15 min after amylin treatment; the effect appeared to be dose-dependent (5–20 μg/kg amylin). A portion of pERK-positive neurons in the AP carried the amylin-receptor and 22% of the pERK-positive neurons were noradrenergic. Pretreatment of rats with U0126 decreased the number of pERK-positive neurons in the AP after amylin injection. U0126 also attenuated the ability of amylin to reduce eating, at least when the animals had been fasted 24 h prior to the feeding trial. Overall, our results suggest that amylin directly stimulates pERK in AP neurons in a time- and dose-dependent manner. Part of the AP neurons displaying pERK were noradrenergic. At least under fasting conditions, pERK was shown to be a necessary part in the signaling cascade mediating amylin's anorectic effect.

Dexamethasone and 8-bromo-cyclic AMP depress the incorporation of [3H]thymidine into mouse condylar cartilage by different pathways

1986 ◽  
Vol 109 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Z. Kraiem ◽  
G. Maor ◽  
M. Silbermann
Keyword(s):  
Cyclic Amp ◽  
Thymidine Incorporation ◽  
Phosphodiesterase Inhibitor ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Condylar Cartilage ◽  
Camp Analogue ◽  
Dose Dependent Fashion ◽  
Cartilage Cells ◽  
Dose Dependent

ABSTRACT We examined whether cyclic AMP (cAMP) affects the incorporation of [3H]thymidine into cartilage cells and, if so, whether this action could be related to the inhibitory effect of glucocorticoid hormones on the growth of ossifying cartilage. Incorporation of [3H]thymidine into trichloroacetic acid-precipitable material by mouse cartilage was measured concomitantly with the concentration of cAMP. Dexamethasone (1 μmol/l) significantly (P < 0·05) depressed the incorporation of [3H]thymidine. The cAMP analogue 8-bromo-cAMP (0·01–1 mmol/l) also depressed the incorporation of the radionucleotide in a dose-dependent fashion. When various concentrations of 8-bromo-cAMP were added with dexamethasone (1 μmol/l), no apparent changes took place compared with the effect of dexamethasone alone. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0·2-1 mmol/l) elicited an inhibitory effect on [3H]thymidine incorporation and a stimulatory influence on cartilage cAMP concentrations. Dexamethasone, at doses (0·01–1 μmol/l) causing significant inhibition of [3H]thymidine incorporation, failed to increase cartilage levels of cAMP. It seems, therefore, that the depressive effect of dexamethasone on [3H]thymidine incorporation in condylar cartilage is not mediated through an increase of cAMP in the tissue. J. Endocr. (1986) 109, 209–213

scholarly journals Impact of Thyme Microcapsules on Histamine Production by Proteus bacillus in Xinjiang Smoked Horsemeat Sausage

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2491
Author(s):  
Honghong Yu ◽  
Yali Huang ◽  
Liliang Lu ◽  
Yuhan Liu ◽  
Zonggui Tang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Antibacterial Activity ◽  
Essential Oil ◽  
Pure Culture ◽  
Histidine Decarboxylase ◽  
Inhibitory Effect ◽  
Gene Expression Level ◽  
Expression Level ◽  
Histamine Concentration ◽  
Histamine Production

Here, we explored the influences of thyme microcapsules on the growth, gene expression, and histamine accumulation by Proteus bacillus isolated from smoked horsemeat sausage. RT-qPCR was employed to evaluate the gene expression level of histidine decarboxylase (HDC) cascade-associated genes. We used HPLC to monitor histamine concentration both in pure culture as well as in the processing of smoked horsemeat sausage. Results showed that histamine accumulation was suppressed by thyme microcapsule inhibitory effect on the histamine-producing bacteria and the reduction in the transcription of hdcA and hdcP genes. Besides, compared with thyme essential oil (EO), thyme microcapsules exhibited higher antibacterial activity and had a higher score for overall acceptance. Therefore, the addition of thyme microcapsules in Xinjiang smoked horsemeat sausage inhibits histamine accumulation.

scholarly journals A role for intracellular histamine in collagen-induced platelet aggregation

Blood ◽  
1990 ◽  
Vol 75 (2) ◽  
pp. 407-414 ◽  
Author(s):  
SP Saxena ◽  
A McNicol ◽  
LJ Brandes ◽  
AB Becker ◽  
JM Gerrard
Keyword(s):  
Platelet Aggregation ◽  
Histidine Decarboxylase ◽  
Histamine Receptor ◽  
Cyclooxygenase Inhibitors ◽  
Histamine Synthesis ◽  
Serotonin Secretion ◽  
Histamine Production ◽  
Thromboxane Production ◽  
Induced Aggregation

Abstract We previously demonstrated that newly formed intracellular histamine mediates platelet aggregation in response to phorbol-12-myristate-13- acetate (PMA). We now report further investigations of the role of histamine during physiological activation of platelets by collagen. Platelets stirred with collagen produced histamine; the rise in histamine precedes the onset of aggregation. The dose response for collagen stimulation of histamine synthesis and platelet aggregation is similar. Inhibitors of histidine decarboxylase (HDC) block both aggregation and histamine synthesis in parallel. Histamine production is not dependent on aggregation; both the intracellular histamine receptor antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine- HCl (DPPE), and the cyclooxygenase inhibitors, aspirin and indomethacin, inhibit collagen-induced aggregation but not histamine synthesis. DPPE also inhibits collagen-induced serotonin secretion and thromboxane production. The effects of DPPE and HDC inhibitors are significantly reversed by the addition of histamine (0.1 to 10 mumol/L) to saponin-permeabilized platelets, though histamine alone has no pro- aggregatory effects. The results suggest that newly synthesized intracellular histamine has a role in collagen-induced platelet activation and that it may act to promote the generation of thromboxane and the secretion responses of platelet granules.

scholarly journals Proinflammatory profile of neonatal monocytes induced by microbial ligands is downmodulated by histamine

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Anna Cláudia Calvielli Castelo Branco ◽  
Nátalli Zanete Pereira ◽  
Fábio Seiti Yamada Yoshikawa ◽  
Luanda Mara da Silva Oliveira ◽  
Franciane Mouradian Emidio Teixeira ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Mononuclear Cells ◽  
Neonatal Period ◽  
Fold Increase ◽  
Histamine Receptor ◽  
Inhibitory Effect ◽  
Human Cord Blood ◽  
Protein Levels ◽  
Genes Encoding ◽  
Cord Blood Cells

Abstract Although the neonatal period is characterized by relative immunological immaturity, an inflammatory response due to Toll-like receptor (TLR) activation is observed. Histamine may be one of the factors playing a role in restraining inflammation during the early stages of life. Therefore, we evaluated the responsiveness of human cord blood cells to TLR4 agonists and the immunomodulatory function of histamine in the inflammatory response. Compared with adults, mononuclear cells (MNCs) from newborns (NBs) exhibit impaired production of IFN-γ-inducible chemokines, such as CXCL10 and CXCL9, upon lipopolysaccharide (LPS) stimulation. Notably, LPS induced a 5-fold increase in CCL2 secretion in NBs. Evaluation of the effect of histamine on LPS-induced CCL2 secretion showed an inhibitory effect in the majority of adults, whereas this effect was detectable in all NBs. Histamine receptor (HR) blockage revealed partial involvement of H1R, H2R and H4R in LPS-induced CCL2 inhibition in MNCs from both NBs and adults. As monocytes are the main type of mononuclear cell that produces CCL2, we evaluated genes related to TLR signaling upon LPS stimulation. Monocytes from NBs showed up-regulation of genes associated with JAK/STAT/NF-κB and IFN signaling. Some differentially expressed genes encoding proinflammatory factors were preferentially detected in LPS-activated monocytes from NBs, and markedly down-regulated by histamine. The immunomodulatory role of histamine on CCL2 and CXCL8 was detected at the transcript and protein levels. Our findings show that NBs have enhanced CCL2 responsiveness to LPS, and that histamine acts in immune homeostasis during the neonatal period to counterbalance the robustness of TLR stimulation.

Gastrin regulates the human histidine decarboxylase promoter through an AP-1-dependent mechanism

1997 ◽  
Vol 272 (4) ◽  
pp. G822-G830 ◽  
Author(s):  
M. Hocker ◽  
Z. Zhang ◽  
J. L. Merchant ◽  
T. C. Wang
Keyword(s):  
B Cells ◽  
Histidine Decarboxylase ◽  
Dominant Negative ◽  
Response Element ◽  
F9 Cells ◽  
Cis Acting ◽  
Dose Dependent Fashion ◽  
F9 Embryonal Carcinoma Cells ◽  
Dose Dependent

The histidine decarboxylase (HDC) gene is regulated transcriptionally by gastrin and phorbol 12-myristate 13-acetate (PMA) through a protein kinase C (PKC)-related pathway. To determine the role of AP-1 (fos/jun) in the regulation of the HDC promoter, gastric cancer (AGS-B) cells stably expressing the cholecystokinin-B/ gastrin receptor and the 1.8-kb human (h) HDC-luciferase (luc) construct were cotransfected with constructs expressing c-fos and c-jun. Overexpression of c-fos and c-jun activated the HDC promoter in a dose-dependent fashion in 1.8-kb hHDC-luc/AGS-B cells as well as in transfected F9 embryonal carcinoma cells, which lack endogenous AP-1 activity. PMA was unable to activate the HDC promoter in F9 cells, which were not transfected with c-fos and c-jun. Gastrin stimulation increased c-fos and c-jun mRNA abundance and AP-1-dependent transcriptional activity, as assessed by a reporter construct in which the CAT reporter gene is under the control of a 12-O-tetradecanoylphorbol-13-acetate response element multimer. Gastrin-stimulated HDC promoter activity was blocked by transfection of c-fos antisense and dominant negative c-jun expression constructs. Finally, overexpression of c-fos and c-jun activated the hHDC promoter through a downstream cis-acting element (gastrin response element), which does not bind AP-1. In conclusion, activation of AP-1 is essential for gastrin-stimulated HDC transcription, but the mechanism appears to be indirect.

Antagonism by theophylline of the adenosine receptor agonist 5′-N-ethykarboxamidoadenosine at the guinea pig ileum

1985 ◽  
Vol 63 (9) ◽  
pp. 1195-1197 ◽  
Author(s):  
F. L. Christofi ◽  
M. A. Cook
Keyword(s):  
Guinea Pig ◽  
Receptor Agonist ◽  
Acetylcholine Release ◽  
Receptor Site ◽  
Inhibitory Effect ◽  
Guinea Pig Ileum ◽  
Competitive Antagonism ◽  
Adenosine Receptor Agonist ◽  
Dose Dependent Fashion ◽  
Dose Dependent

The inhibitory effect of the putative adenosine A2 receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) on acetylcholine release from the stimulated guinea pig ileum preparation and the nature of its antagonism by theophylline were investigated. NECA was shown to inhibit the response of the ileum preparation in a dose-dependent fashion, and an EC50 value of 1.62 × 10−8 M was determined. This value was comparable with that determined for the A1 receptor agonist N6-R-phenylisopropyladenosine (R-PIA) (2.57 × 10−8 M) using the same preparation. Competitive antagonism of the inhibitory effect of NECA by theophylline was quantitated and a pA2 value of 5.04 for the methylxanthine was obtained. This value was similar to those obtained previously for R-PIA and adenosine itself and suggests that these nucleosides may be interacting with the same receptor site on myenteric nerve endings. These findings do not permit the designation of the receptor as an A1 or A2 subtype according to current criteria.

scholarly journals A role for intracellular histamine in collagen-induced platelet aggregation

Blood ◽  
1990 ◽  
Vol 75 (2) ◽  
pp. 407-414
Author(s):  
SP Saxena ◽  
A McNicol ◽  
LJ Brandes ◽  
AB Becker ◽  
JM Gerrard
Keyword(s):  
Platelet Aggregation ◽  
Histidine Decarboxylase ◽  
Histamine Receptor ◽  
Cyclooxygenase Inhibitors ◽  
Histamine Synthesis ◽  
Serotonin Secretion ◽  
Histamine Production ◽  
Thromboxane Production ◽  
Induced Aggregation

We previously demonstrated that newly formed intracellular histamine mediates platelet aggregation in response to phorbol-12-myristate-13- acetate (PMA). We now report further investigations of the role of histamine during physiological activation of platelets by collagen. Platelets stirred with collagen produced histamine; the rise in histamine precedes the onset of aggregation. The dose response for collagen stimulation of histamine synthesis and platelet aggregation is similar. Inhibitors of histidine decarboxylase (HDC) block both aggregation and histamine synthesis in parallel. Histamine production is not dependent on aggregation; both the intracellular histamine receptor antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine- HCl (DPPE), and the cyclooxygenase inhibitors, aspirin and indomethacin, inhibit collagen-induced aggregation but not histamine synthesis. DPPE also inhibits collagen-induced serotonin secretion and thromboxane production. The effects of DPPE and HDC inhibitors are significantly reversed by the addition of histamine (0.1 to 10 mumol/L) to saponin-permeabilized platelets, though histamine alone has no pro- aggregatory effects. The results suggest that newly synthesized intracellular histamine has a role in collagen-induced platelet activation and that it may act to promote the generation of thromboxane and the secretion responses of platelet granules.

Suppression of the Cerebral Vasospastic Actions of Oxyhemoglobin by Ascorbic Acid

Neurosurgery ◽  
1991 ◽  
Vol 28 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Masahisa Kawakami ◽  
Namio Kodama ◽  
Noboru Toda
Keyword(s):  
Ascorbic Acid ◽  
Biological Activity ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Arteries ◽  
Inhibitory Effect ◽  
Cisternal Irrigation ◽  
Dose Dependent Fashion ◽  
Anesthetized Dogs ◽  
Dose Dependent ◽  
Stimulation Of

Abstract Oxyhemoglobin (Oxy-Hb) produced a concentration-dependent contraction of monkey, dog, and bovine cerebral artery strips. Treatment of Oxy-Hb with ascorbic acid suppressed the ability of Oxy-Hb to contract the arteries, especially in the monkey arteries. The ability of intracisternally applied Oxy-Hb to constrict the basilar artery in anesthetized dogs was diminished when Oxy-Hb was treated previously with ascorbic acid (AsA-Hb). The contraction caused by Oxy-Hb was suppressed by treatment with indomethacin and aspirin in isolated bovine cerebral arteries. Endothelium-dependent relaxations elicited by substance P and relaxations induced by stimulation of the vasodilator nerves with nicotine were suppressed by treatment with Oxy-Hb and AsA-Hb; however, the inhibitory effect of AsA-Hb was markedly less. Oxy-Hb attenuated nitroglycerin-induced relaxations in a dose-dependent fashion, whereas AsA-Hb in concentrations up to 1.6 x 10-5 M did not significantly influence the relaxations. It is concluded that incubation of Oxy-Hb with ascorbic acid alters markedly the biological activity of Oxy-Hb; the vasoconstrictor activity is suppressed, and the ability to diminish vasodilator actions is minimized. These findings provide a rationale for the use of ascorbic acid in cisternal irrigation to prevent the development of cerebral vasospasm after a subarachnoid hemorrhage.

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