Associations of Polymorphisms in Histidine Decarboxylase,Histamine N-Methyltransferase and Histamine Receptor H3 Genes with Breast Cancer

We previously found that genetic polymorphisms in gene coding for histamine H₄ receptors were related to the risk and malignant degree of breast cancer. The roles of polymorphisms in other histamine-related genes, such as histidine decarboxylase (HDC), histamine N-methyltransferase (HNMT) and histamine H₃ receptor (HRH3), remain unexplored. The aim of this study is to analyze the clinical associations of polymorphisms in HDC, HNMT and HRH3 with breast cancer. Two hundred and one unrelated Chinese Han breast cancer patients and 205 ethnicity-matched health controls were recruited for case-control investigation. Genomic DNA from the participants was extracted and 5 single nucleotide polymorphisms (SNPs) in HDC, HNMT and HRH3 were genotyped. We found that polymorphisms of HNMT and HRH3 were irrelevant with breast cancer in the present study. However, the T allele of rs7164386 in HDC significantly decreased the risk of breast cancer (adjusted odds ratios [ORs], 0.387; 95% confidence intervals [CIs], 0.208–0.720; P = 0.003). Furthermore, for HDC haplotypes, the CG haplotype of rs7164386-rs7182203 was more frequent among breast cancer patients (adjusted OR, 1.828; 95% CI, 1.218–2.744; P = 0.004) while the TG haplotype was more frequent among health controls (adjusted OR, 0.351; 95% CI, 0.182–0.678; P = 0.002). These findings indicated that polymorphisms of HDC gene were significantly associated with breast cancer in Chinese Han population and may be novel diagnostic or therapeutic targets for breast cancer. Further studies with larger participants worldwide are still needed for conclusion validation.     

Histamine Receptor Expression, Hippocampal Plasticity and Ammonia in Histidine Decarboxylase Knockout Mice

Genetic ablation of the histamine producing enzyme histidine decarboxylase (HDC) leads to alteration in exploratory behaviour and hippocampus-dependent learning. We investigated how brain histamine deficiency in HDC knockout mice (HDC KO) affects hippocampal excitability, synaptic plasticity, and the expression of histamine receptors. No significant alterations in: basal synaptic transmission, long-term potentiation (LTP) in the Schaffer collateral synapses, histamine-induced transient changes in the CA1 pyramidal cell excitability, and the expression of H1 and H2 receptor mRNAs were found in hippocampal slices from HDC KO mice. However, when compared to WT mice, HDC KO mice demonstrated: 1. a stronger enhancement of LTP by histamine, 2. a stronger impairment of LTP by ammonia, 3. no long-lasting potentiation of population spikes by histamine, 4. a decreased expression of H3 receptor mRNA, and 5. less potentiation of population spikes by H3 receptor agonism. Parallel measurements in the hypothalamic tuberomamillary nucleus, the origin of neuronal histamine, demonstrated an increased expression of H3 receptors in HDC KO mice without any changes in the spontaneous firing of “histaminergic” neurons without histamine and their responses to the H3 receptor agonist (R)-α-methylhistamine. We conclude that the absence of neuronal histamine results in subtle changes in hippocampal synaptic transmission and plasticity associated with alteration in the expression of H3 receptors.     

Evolution and Multiplicity of Arginine Decarboxylases in Polyamine Biosynthesis and Essential Role in Bacillus subtilis Biofilm Formation

Arginine decarboxylases (ADCs; EC 4.1.1.19) from four different protein fold families are important for polyamine biosynthesis in bacteria, archaea, and plants. Biosynthetic alanine racemase fold (AR-fold) ADC is widespread in bacteria and plants. We report the discovery and characterization of an ancestral form of the AR-fold ADC in the bacterial Chloroflexi and Bacteroidetes phyla. The ancestral AR-fold ADC lacks a large insertion found in Escherichia coli and plant AR-fold ADC and is more similar to the lysine biosynthetic enzyme meso-diaminopimelate decarboxylase, from which it has evolved. An E. coli acid-inducible ADC belonging to the aspartate aminotransferase fold (AAT-fold) is involved in acid resistance but not polyamine biosynthesis. We report here that the acid-inducible AAT-fold ADC has evolved from a shorter, ancestral biosynthetic AAT-fold ADC by fusion of a response regulator receiver domain protein to the N terminus. Ancestral biosynthetic AAT-fold ADC appears to be limited to firmicute bacteria. The phylogenetic distribution of different forms of ADC distinguishes bacteria from archaea, euryarchaeota from crenarchaeota, double-membraned from single-membraned bacteria, and firmicutes from actinobacteria. Our findings extend to eight the different enzyme forms carrying out the activity described by EC 4.1.1.19. ADC gene clustering reveals that polyamine biosynthesis employs diverse and exchangeable synthetic modules. We show that in Bacillus subtilis, ADC and polyamines are essential for biofilm formation, and this appears to be an ancient, evolutionarily conserved function of polyamines in bacteria. Also of relevance to human health, we found that arginine decarboxylation is the dominant pathway for polyamine biosynthesis in human gut microbiota.     

金枪鱼肉中组胺菌的分离及其理化性质分析

目的：对金枪鱼肉中的组胺生成菌进行生化实验和功能酶检测,进而对鱼肉中组胺菌的存在提供可参考数据。方法：利用组氨酸肉汤培养液,对金枪鱼肉中的组胺生成菌进行筛选,然后通过生物化学实验和形态学实验,进而对组胺生成菌进行分析。结果：分离得到2株组胺菌,菌种Ⅰ在5℃~30℃的培养温度范围内,随温度升高,组胺生成量逐渐增加,在30℃有最高组胺生成量,约2 700ppm。菌种Ⅱ在25℃有组胺最高生成量约为2 400ppm。结论：依据两种组胺菌的特征和生理生化特征,分离菌可能分别属于弧菌属、埃希氏菌属。     

Dexamethasone Inhibits Mitogen-dependent Synthesis of Histamine Due to Histidine Decarboxylase Induced in Cultured Mouse Spleen Cells

Schizosaccharomyces pombe has four α-amylase homologs (Aah1p-Aah4p) with a glycosylphosphatidylinositol (GPI) modification site at the C-terminal end. Disruption mutants of aah genes were tested for mislocalization of vacuolar carboxypeptidase Y (CPY), and aah3Δ was found to secrete CPY. The conversion rate from pro- to mature CPY was greatly impaired in aah3Δ, and fluorescence microscopy inidicated that a sorting receptor for CPY, Vps10p, mislocalized to the vacuolar membrane. These results indicate that aah3Δ had a defect in the retrograde transport of Vps10p, and that Aah3p is the first S. pombe specific protein required for vacuolar protein sorting.     

Study of Microflora in Malaysian Dried Fishes and Their Decontamination by Gamma-irradiation

The distribution of microorganisms in 10 samples of salted dried fish and the effects of irradiation of them were studied. The total aerobic bacteria in commercial dried fish were determined to be from 2 × 10⁴ to 3 × 10⁶ per gram. Mold counts were 1 × 10² to 7 × 10³ per gram with a lower amount of yeasts. In spoiled dried fish, total aerobic bacteria were determined to be 4× 10⁶ or 1 × 10⁷ per gram with a few yeasts. Coliforms were not isolated on MacConkey agar plates from any of the samples. The predominant bacteria occurring in spoiled dried fish were Pediococcus halophilus, Vibrio costicola and Planococcus sp. More than 50% of the molds consisted of the Aspergillus niger group, whereas lower amounts of the A. flavus, A. fumigatus and A. ochraceus groups, Penicillium chrysogenum series, etc. were also isolated from many samples of dried fish. All kinds of putrefactive microorganisms were radiation sensitive, and a dose of ca. 500 krad appears to be sufficient for extension of the shelf-life of dried fish from 2 to 4 times.     

葡萄果实中的糖分积累和调控

文章介绍葡萄果实不同发育期糖分积累的特点.糖分积累的细胞学途径、共质体到质外体的转变过程和这两种途径的调控机制,以及根域限制栽培措施对葡萄果实糖分积累的影响和机制的研究进展.     

The Role of Histidine in the Ligand-Bonding Capacity of the Hemoglobin Gene

The atomic and electronic structures of heme complexes with His, Gly, and Cys residues (Heme–His, Heme–Gly, and Heme–Cys) in the fifth coordination position of the Fe atom and with oxygen and nitrogen oxide molecules in the sixth Fe position were studied by the semiempirical quantum-chemical method PM3. A comparative analysis of internuclear distances showed that the strength of chemical bonding between the ligand molecules (oxygen and nitrogen oxide) is greater for Heme–Cys than for Heme–His and Heme–Gly complexes. Consequently, the strengthening of the chemical bond of the oxygen (or nitrogen oxide) molecule with Heme–Cys substantially weakens the chemical bond in the ligand molecule. The Mulliken population analysis showed that the electronic density of ligand (oxygen or nitrogen oxide) p-orbitals is transferred to the d-orbitals of the Fe atom, whose charge, calculated according to the Mulliken analysis, formally becomes negative. In the Heme–His complex with oxygen, this charge is substantially greater than in the complex with NO, and the oxygen molecule becomes polarized. No oxygen polarization is observed in the Heme–Cys complex, and the electron density (judging from the change in the Fe charge) is transferred to the coordinated sulfur atom. This is also characteristic of Heme–Cys complexes with nitrogen oxide. An analysis of charges on the atoms indicates that the character of chemical bonding of the oxygen molecule in Heme–Cys and Heme–Gly complexes is similar and basically differs from that in the case of the Heme–His complex.     

柑橘果实的光合特性、产物运输及分配在糖分积累中的作用

测定了温州蜜柑 (CitrusunshiuMarc .cv .Miyagawawase)果实发育进程中干鲜重、果皮光合速率和叶绿素含量的变化 ,并用14 CO2 示踪技术研究了果皮和叶同化生成的光合产物在果实内的运输分配特性。结果表明 :果皮光合速率与叶绿素含量有关 ,随着叶绿素含量的下降 ,果实光合速率也快速下降。在果实完熟之前 ,即使是当果皮积累的干重超过汁囊时 ,叶同化产物仍主要分配到汁囊中 ;而在完熟阶段 ,果皮光合速率接近零 ,果皮成了叶同化产物的主要库。果皮的同化产物 ,主要保留在果皮中 ,输入到汁囊的比率随果实发育而下降 ,但高峰时也有 12 %输入汁囊。与对照相比 ,果实遮光处理后降低了果皮与汁囊的干重和含糖量。上述结果表明果皮光合产物主要用于果皮自身的发育并能减少对叶光合产物的依赖 ,同时也能部分增加汁囊糖的积累     

Histamine Stimulation of Cyclic AMP Accumulation in Astrocyte-Enriched and Neuronal Primary Cultures from Rat Brain

Histamine stimulates cyclic AMP accumulation in astrocyte-enriched and neuronal primary cultures from rat brain in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine. The response in the astrocyte cultures (Emax = 304 +/- 44% over basal, EC50 = 43 +/- 5 microM) was much higher than in neuronal cultures (Emax = 24 +/- 2%, EC50 = 14 +/- 7 microM). The histamine effect in astrocytes was competitively inhibited by the H2 antagonists cimetidine (Ki = 1.1 +/- 0.2 microM) and ranitidine (Ki = 46 +/- 10 nM) but was insensitive to the H1 antagonist mepyramine (1 microM). The two selective H2 agonists impromidine and dimaprit behaved as partial agonists and showed relative potencies (139 and 0.5, respectively) consistent with an interaction with H2 receptors. The more selective H1 agonist 2-thiazolylethylamine (0.01-1 mM) did not potentiate the response to impromidine (10 microM). Thus, in contrast to what is generally observed in intact cell preparations from brain, the histamine-induced cyclic AMP accumulation in astroglial cells is mediated solely by H2 receptors. The small effect shown in neuronal cultures also appears to be mediated by H2 receptors.     

Understanding the Role of Histidine in the GHSxG Acyltransferase Active Site Motif: Evidence for Histidine Stabilization of the Malonyl-Enzyme Intermediate

Acyltransferases determine which extender units are incorporated into polyketide and fatty acid products. The ping-pong acyltransferase mechanism utilizes a serine in a conserved GHSxG motif. However, the role of the conserved histidine in this motif is poorly understood. We observed that a histidine to alanine mutation (H640A) in the GHSxG motif of the malonyl-CoA specific yersiniabactin acyltransferase results in an approximately seven-fold higher hydrolysis rate over the wildtype enzyme, while retaining transacylation activity. We propose two possibilities for the reduction in hydrolysis rate: either H640 structurally stabilizes the protein by hydrogen bonding with a conserved asparagine in the ferredoxin-like subdomain of the protein, or a water-mediated hydrogen bond between H640 and the malonyl moiety stabilizes the malonyl-O-AT ester intermediate.     

Novel Histamine Measurement by HPLC Analysis Used to Assay Histidine Decarboxylase Inhibitory Activity of Shoyuflavones from Soy Sauce

An easy and highly sensitive method for measuring histamine by HPLC analysis coupled with precolumn derivatization was established. The amino group of histamine was completely colorimetrically labelled with 4-N,N-dimethylamino-azobenzene-4′-isothiocyanate (DABITC) in the presence of sodium bicarbonate at 90°C for 5 min. The derivative was sensitively and easily analyzed by HPLC on a Cosmosil 5SL column using CHCl₃/N,N-dimethylformamide/H₂O (210:90:4) containing 0.4% acetic acid. Using the established method, histidine decarboxylase (HDC) inhibitory activities of three tartaric acid isoflavone derivatives, named shoyuflavones, isolated from soy sauce were examined in vitro by measuring the histamine produced by HDC. They showed intense inhibition of the activities of HDC from both mouse mastocytoma P-815 cells and Clostridium perfringens.     

Hedgerows and Their Role in Agricultural Landscapes

Hedgerows, rows of trees or shrubs enclosing or separating fields, are man made. They are part of rural landscapes and should not be studied without considering the farming systems and the rural society as a whole. Their species composition depends on the history of the countryside, as well as current farming practices. Land use and boundary management play a major role in determining the floristic composition of hedgerows, and are strongly related to the grain size of the field's mosaic. Hedgerow networks, due to their rectilinear shape, and with their high degree of connection, enhance or interrupt many fluxes in the landscape. Hedgerows act as a corridor of movement and dispersal for many forest species, such as carabids, small mammals, and plants. On the other hand, hedgerows interrupt or slow down air fluxes and the propagules they carry. In the heterogeneous mosaic of fields and wooded patches, hedgerows often increase the functional connectivity of rural landscapes. The future of hedgerows depends on the changes of the rural society, which includes more and more nonfarmers. Hedgerows will be considered not only as a part of a productive area, but also as an element of a multifunctional landscape.     

Aldehyde Dehydrogenases and Their Role in Carcinogenesis

Abstract

Aldehydes are highly reactive molecules that may have a variety of effects on biological systems. They can be generated from a virtually limitless number of endogenous and exogenous sources. Although some aldehyde-mediated effects such as vision are beneficial, many effects are deleterious, including cytotoxicity, mutagenicity, and carcinogenicity. A variety of enzymes have evolved to metabolize aldehydes to less reactive forms. Among the most effective pathways for aldehyde metabolism is their oxidation to carboxylic acids by aldehyde dehydrogenases (ALDHs).

ALDHs are a family of NADP-dependent enzymes with common structural and functional features that catalyze the oxidation of a broad spectrum of aliphatic and aromatic aldehydes. Based on primary sequence analysis, three major classes of mammalian ALDHs — 1, 2, and 3 — have been identified. Classes 1 and 3 contain both constitutively expressed and inducible cytosolic forms. Class 2 consists of constitutive mitochondrial enzymes. Each class appears to oxidize a variety of substrates that may be derived either from endogenous sources such as amino acid, biogenic amine, or lipid metabolism or from exogenous sources, including aldehydes derived from xenobiotic metabolism.

Changes in ALDH activity have been observed during experimental liver and urinary bladder carcinogenesis and in a number of human tumors, including some liver, colon, and mammary cancers. Changes in ALDH define at least one population of preneoplastic cells having a high probability of progressing to overt neoplasms. The most common change is the appearance of class 3 ALDH dehydrogenase activity in tumors arising in tissues that normally do not express this form. The changes in enzyme activity occur early in tumorigenesis and are the result of permanent changes in ALDH gene expression.

This review discusses several aspects of ALDH expression during carcinogenesis. A brief introduction examines the variety of sources of aldehydes. This is followed by a discussion of the mammalian ALDHs. Because the ALDHs are a relatively understudied family of enzymes, this section presents what is currently known about the general structural and functional properties of the enzymes and the interrelationships of the various forms.

The remainder of the review discusses various aspects of the ALDHs in relation to tumorigenesis. The expression of ALDH during experimental carcinogenesis and what is known about the molecular mechanisms underlying those changes are discussed. This is followed by an extended discussion of the potential roles for ALDH in tumorigenesis. The role of ALDH in the metabolism of cyclophosphamidelike chemotherapeutic agents is described. This work suggests that modulation of ALDH activity may be an important determinant of the effectiveness of certain chemotherapeutic agents. The evidence that changes in ALDH are part of an adaptive response of preneoplastic and neoplastic cells to altered cell physiology or stress is then considered. Roles in the metabolism of aldehydes generated from lipid peroxidation and as part of the Ah gene-mediated response to xenobiotic exposure are both discussed. The data are consistent with a role for certain ALDHs in lipid aldehyde metabolism. Biochemical and genetic data also imply that changes in ALDH may be linked, in part, to cellular adaptation to oxidative stress.

Finally, a model of inducible ALDH gene regulation is proposed. The model incorporates current information about ALDH gene expression with the regulation of other genes known to be part of the adaptive responses occurring in neoplastic cells. The model suggests that regulation of class 1 and 3 ALDH gene activity may be complex, involving the tissue-specific ability to respond to a variety of physiological cues. The model also suggests several avenues for future research that should provide a clearer understanding of the regulation of this important gene family in response to a variety of factors.     

Role of Histidine 932 of the Human Mitochondrial DNA Polymerase in Nucleotide Discrimination and Inherited Disease

The human mitochondrial DNA polymerase (pol γ) is nuclearly encoded and is solely responsible for the replication and repair of the mitochondrial genome. The progressive accumulation of mutations within the mitochondrial genome is thought to be related to aging, and mutations in the pol γ gene are responsible for numerous heritable disorders including progressive external opthalmoplegia, Alpers syndrome, and parkinsonism. Here we investigate the kinetic effect of H932Y, a mutation associated with opthalmoplegia. Mutations H932Y and H932A reduce the specificity constant governing correct nucleotide incorporation 150- and 70-fold, respectively, without significantly affecting fidelity of incorporation or the maximum rate of incorporation. However, this leads to only a 2-fold reduction in rate of incorporation at a physiological nucleotide concentration (∼100 μm). Surprisingly, incorporation of T:T or C:T mismatches catalyzed by either H932Y or H932A mutants was followed by slow pyrophosphate release (or fast pyrophosphate rebinding). Also, H932Y readily catalyzed incorporation of multiple mismatches, which may have a profound physiological impact over time. His-932 is thought to contact the β-phosphate of the incoming nucleotide, so it is perhaps surprising that H932Y appears to slow rather than accelerate pyrophosphate release.     

On the Role of Histamine Receptors in the Regulation of Circadian Rhythms

Several lines of evidence suggest a regulatory role of histamine in circadian rhythms, but little is known about signaling pathways that would be involved in such a putative role. The aim of this study was to examine whether histamine mediates its effects on the circadian system through Hrh1 or Hrh3 receptors. We assessed both diurnal and free-running locomotor activity rhythms of Hrh1 ^-/- and Hrh3 ^-/- mice. We also determined the expression of Per1, Per2 and Bmal1 genes in the suprachiasmatic nuclei, several areas of the cerebral cortex and striatum under symmetric 24 h light-dark cycle at zeitgeber times 14 and 6 by using radioactive in situ hybridization. We found no differences between Hrh1 ^-/- and wild type mice in the length, amplitude and mesor of diurnal and free-running activity rhythms as well as in expression of Per1, Per2 and Bmal1 genes in any of the examined brain structures. The amplitude of free-running activity rhythm of the Hrh3 ^-/- mice was significantly flattened, whereas the expression of the clock genes in Hrh3 ^-/- mice was similar to the wild type animals in all of the assessed brain structures. Therefore, the knockout of Hrh1 receptor had no effects on the circadian rhythm of spontaneous locomotion, and a knockout of Hrh3 receptor caused a substantial reduction of free-running activity rhythm amplitude, but none of these knockout models affected the expression patterns of the core clock genes in any of the studied brain structures.     

果实中糖的运输、代谢与积累及其调控

叶片光合产物向果实运输的主要形态是蔗糖,但在木本蔷薇科果树中,光合产物的主要运输形态为山梨醇.糖从质外体空间跨膜运入共质体的过程由糖运输蛋白介导,而糖运输蛋白的基因表达伴随着果实糖的积累而增强.蔗糖代谢酶参与了细胞内外4个与糖运输有关的无效循环.己糖代谢抑制是果实糖快速积累的前提.在木本蔷薇科果实中,蔗糖代谢酶活力仍非常活跃,表明蔗糖可能与山梨醇在果实生长发育中都起重要的作用.糖作为信号分子,调节了承担糖运输与代谢的基因的表达.自然环境因子和栽培措施能有效调控糖运输、代谢与积累.反义抑制Ivr基因表达能提高番茄果实含糖量的实验结果表明遗传工程调控糖积累的潜力.阐明糖信号与其它信号互作对糖运输与代谢的调控机制是今后研究的重点.