Disease relevance of HDC

• Previously, we demonstrated that gastrin activates HDC promoter activity in a gastric cancer (AGS-E) cell line through three overlapping downstream promoter elements [1].
• Quantitative real time PCR revealed that chronic urticaria expresses high levels of CRH-R1 and HDC as compared to normal foreskin, breast skin and cultured human keratinocytes [2].
• Histamine content and HDC activity were determined in 10 specimens of nasal polyp, nine specimens of maxillary sinus and five specimens of inferior turbinate [3].
• In previous studies we have detected the expression of the l-histidine decarboxylase (HDC) gene and the presence of HDC protein in human melanoma cell lines [4].
• On the other hand, bronchial carcinoids and lung PDNECs showed high DDC mRNA levels, but nearly undetectable HDC mRNA levels [5].

High impact information on HDC

• Recent work indicates physiological regulation of the expression of genes encoding cytosolic enzymes such as histidine decarboxylase, which converts histidine to histamine, and of secretory granule transporters such as vesicular monoamine transporter type 2, which concentrates amines in secretory vesicles [6].
• In saponin-permeabilized platelets, added histamine reversed the inhibition by DPPE or HDC inhibitors on aggregation induced by PMA or collagen [7].
• The infusion decreased plasma gastrin and gastrin synthesis; moreover, there were marked reductions in markers of ECL cell function, e.g., histidine decarboxylase and chromogranin A messenger RNA abundance, in carcinoid tumor tissue and macroscopically normal corpus mucosa [8].
• It is suggested that an octreotide supression test coupled with assay of histidine decarboxylase or chromogranin A gene expression is useful in the assessment of gastric carcinoid tumors [8].
• CONCLUSIONS: H. pylori is the main source of gastric N alpha-MeHA that may lower histidine decarboxylase activity and somatostatin content through H3 receptors [9].

Chemical compound and disease context of HDC

• An injection of Escherichia coli lipopolysaccharide increased the activity of histidine decarboxylase in bone marrow cells in C3H/HeN mice to a much greater extent than in C3H/HeJ mice, which are resistant to various effects of lipopolysaccharide [10].
• Pentagastrin induced a significant increase in histidine decarboxylase activity of the oxyntic gland mucosa with the most profound increase seen in patients with duodenal ulcer [11].
• EXPERIMENTAL DESIGN: Expression/activity of histidine decarboxylase, histamine content, and prostaglandin E2 (PGE2) production were analyzed in 33 colorectal cancer samples and in the HT29, Caco-2, and HCT116 colon cancer cell lines [12].
• Alpha-fluoromethylhistidine (alpha-FMH), a new irreversible inhibitor of mammalian histidine decarboxylase, was tested in the treatment of idiopathic cold urticaria in 11 patients [13].
• Pyridoxal phosphate-dependent histidine decarboxylase from Morganella AM-15 [14].

Biological context of HDC

• Taken together, these results indicate that KLF4 can act to repress HDC gene expression by Sp1-dependent and -independent mechanisms [1].
• Western blotting analysis showed a cross-reaction between anti-HDC and anti-DDC antibodies [5].
• We found a TATA-like sequence, a GC box, four CACC boxes, four GATA consensus sequences, and six leader-binding protein-1 binding motifs in the promoter region of the HDC gene [15].
• Finally, deletion analysis demonstrated that the H2O2 response element could be mapped to the GAS-RE (nucleotides 2 to 24) of the basal HDC promoter [16].
• The transcription start site of the HDC gene and the nucleotide sequences of the promoter and first exon regions were determined [15].

Anatomical context of HDC

• Histidine decarboxylase (HDC) is the enzyme that catalyzes the conversion of histidine to histamine, a bioamine that plays an important role in allergic responses, inflammation, neurotransmission, and gastric acid secretion [1].
• There were no significant differences in HDC activities among three kinds of nasal mucosa [3].
• MATERIAL AND TREATMENT: Human elutriated monocytes from healthy volunteers were incubated with macrophage colony stimulating factor (M-CSF) and the expression of HDC was followed at both mRNA and protein levels [17].
• We provide evidence that enhanced HDC activity reflects the basophil rather than the megakaryocytic differentiation potential of UT7DI cells [18].
• RT-PCR and immunohistochemical staining revealed that the HDC gene was expressed in monocytes/macrophages and T cells in the arterial intima but not in smooth muscle cells in either the arterial intima or the media [19].

Associations of HDC with chemical compounds

• To study the mechanism through which oxidant stress affects gastric cells, we examined the effects of hydrogen peroxide (H2O2) on HDC promoter activity and intracellular signaling in AGS-B cells [16].
• H2O2 (10 mM) specifically activated the HDC promoter 10-12-fold, and this activation was blocked by both mannitol and N-acetylcysteine [16].
• Histidine decarboxylase (HDC) is the enzyme that converts histidine to histamine, a bioamine that plays an important role in many physiological aspects including allergic responses, inflammation, neurotransmission, and gastric acid secretion [20].
• In rats, marked elevation of gastric HDC mRNA abundance was observed within 12 h after induction of hypergastrinemia by a single injection of the proton-pump blocker omeprazole [21].
• Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells [22].

Physical interactions of HDC

• We further showed that KLF4 inhibits HDC promoter activity by competing with Sp1 at the upstream GC box and also independently by binding the three downstream gastrin responsive elements [1].

Regulatory relationships of HDC

• A luciferase promoter assay with U937 and Jurkat cells demonstrated that interleukin-4 (IL-4) inhibited the expression of the HDC gene [19].
• Yin yang 1 (YY1) represses histidine decarboxylase gene expression with SREBP-1a in part through an upstream Sp1 site [20].

Other interactions of HDC

• The lichen simplex samples had high expression of CRH-R1, but low HDC [2].
• The mean values of histamine content and activities of HDC, HMT and histaminase of human nasal mucosa were 137.3 nmol/g wet weight, 26.3 fmol/min/mg protein, 26.4 pmol/min/mg protein and 0.5 pmol/min/mg protein, respectively [3].
• HDC activity was found in WM35 and WM983 cell lines, while detectable HNMT activity was measured in WM983, M1 and HT168 lines [4].
• Western blotting analysis was performed to verify the specificity of anti-DDC and anti-HDC antibodies [5].
• Furthermore, we studied the effect of interleukin (IL)-4, which inhibits the HDC expression, on the expression of MCP-1 and CCR2 [23].

Analytical, diagnostic and therapeutic context of HDC

• Real-time RT-PCR was performed using specific probes for HDC and DDC on 42 cases, examined also for DDC IR [5].
• In situ hybridization with an HDC probe revealed that the expression of the HDC gene in SSc was greater than in normal controls [24].
• After fractionation of monocyte homogenates in a discontinuous Percoll gradient or by differential centrifugation more than 80% of both, HDC activity and histamine, were recovered from the cytosolic fractions [25].
• Sequence analysis revealed that the observed bands were the appropriate HDC amplicons [26].
• Gastric and duodenal biopsies from a patient with anti-histidine decarboxylase antibodies were studied by immunohistochemistry [22].

References