bims-polyam 2019-06-30 papers

on Polyamines

Issue of 2019–06–30
seven papers selected by
Sebastian J. Hofer, University of Graz and Alexander Ivanov, Engelhardt Institute of Molecular Biology

ODC1 promotes proliferation and mobility via the AKT/GSK3β/β-catenin pathway and modulation of acidotic microenvironment in human hepatocellular carcinoma.
Polyamines delay leaf maturation in low-alkaloid tobacco varieties.
Simultaneous determination of eight underivatized biogenic amines in salted mackerel fillet by ion-pair solid-phase extraction and volatile ion-pair reversed-phase liquid chromatography-tandem mass spectrometry.
Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon's Fibroblasts.
Conservation of Thermospermine Synthase Activity in Vascular and Non-vascular Plants.
Polyamine Oxidases Play Various Roles in Plant Development and Abiotic Stress Tolerance.
Function and Regulation of Acid Resistance Antiporters.

Onco Targets Ther. 2019 ;12 4081-4092

ODC1 promotes proliferation and mobility via the AKT/GSK3β/β-catenin pathway and modulation of acidotic microenvironment in human hepatocellular carcinoma.

Zi Ye, Zhirui Zeng, Yiyi Shen, Qiang Yang, Duidui Chen, Zubing Chen, Shiqiang Shen.

  Purpose: Ornithine decarboxylase 1 (ODC1)-an oncogene involved in the biosynthesis of polyamines-is commonly upregulated and associated with poor prognosis in numerous cancers. However, the role and mechanism of ODC1 in hepatocellular carcinoma (HCC) remains unclear. The aim of the present study was to investigate the role of ODC1 in HCC and clarify the latent molecular mechanisms. Material and methods: We used samples obtained from The Cancer Genome Atlas. The expression of ODC1 was also assessed in our additional HCC samples and HCC cell lines. The roles of ODC1 in HCC cell proliferation, migration and invasion in vitro were investigated using the cell-counting kit-8 assay, 5-ethynyl-2´-deoxyuridine assay, colony formation assay, flow cytometry, wound healing assay and transwell assay, respectively. The effect of ODC1 on HCC cell proliferation in vivo was investigated by constructing a xenotransplanted tumor model in nude mice. Quantitative real-time polymerase chain and western blotting were used to detect the expression levels of ODC1 in mimetic hypoxia, nutrient depleted, and acidotic microenvironment. The relationships between ODC1, the AKT/GSK3β/β-catenin pathway, and acidotic microenvironment were further investigated through western blotting, immunohistochemical staining, and immunofluorescence. Results: ODC1 was upregulated in HCC tissues and cell lines, and co-expressed with KI67 and PCNA (P<0.05). A decrease in the expression of ODC1 inhibits proliferation, migration, invasion, and induces cell cycle arrest in HCC cell lines in vitro, while suppressing HCC cell proliferation in vivo (P<0.05). Furthermore, the expression of ODC1 was increased in the mimetic acidotic microenvironment, while the interference with the expression of ODC1 reversed the effect of the acidotic microenvironment through regulation of AKT/GSK3β/β-catenin and related downstream proteins. Conclusion: ODC1 is an unfavorable gene in HCC patients,promoting HCC cell proliferation, migration and invasion via the AKT/GSK3β/β-catenin pathway and modulation of the acidotic microenvironment.

Keywords:  acidotic; hepatocellular carcinoma; ornithine decarboxylase 1; β-catenin

DOI:  https://doi.org/10.2147/OTT.S198341
Plant Direct. 2018 Jul;2(7): e00077

Polyamines delay leaf maturation in low-alkaloid tobacco varieties.

Greta Nölke, Daniel Volke, Ivana Chudobová, Marcel Houdelet, Marcos Lusso, Jesse Frederick, Andrew Adams, Chengalrayan Kudithipudi, Ujwala Warek, James A Strickland, Dongmei Xu, Helga Schinkel, Stefan Schillberg.

  The development of low-alkaloid (LA) tobacco varieties is an important target in the tobacco breeding industry. However, LA Burley 21 plants, in which the Nic1 and Nic2 loci controlling nicotine biosynthesis are deleted, are characterized by impaired leaf maturation that leads to poor leaf quality before and after curing. Polyamines are involved in key developmental, physiological, and metabolic processes in plants, and act as anti-senescence and anti-ripening regulators. We investigated the role of polyamines in tobacco leaf maturation by analyzing the free and conjugated polyamine fractions in the leaves and roots of four Burley 21 varieties: NA (normal alkaloid levels, wild-type control), HI (high intermediates, nic2 -), LI (low intermediates, nic1 -), and LA (nic1 - nic2 -). The pool of conjugated polyamines increased with plant age in the roots and leaves of all four varieties, but the levels of free and conjugated putrescine and spermidine were higher in the LI and LA plants than NA controls. The increase in the polyamine content correlated with delayed maturation and senescence, i.e., LA plants with the highest polyamine levels showed the most severe impaired leaf maturation phenotype, characterized by higher chlorophyll content and more mesophyll cells per unit leaf area. Treatment of LA plants with inhibitors of polyamine biosynthesis and/or the growth regulator Ethephon® reduced accumulation of polyamines, achieving a partial amelioration of the LA phenotype. Our data show that the regulation of polyamine homeostasis is strongly disrupted in LA plants, and that free and conjugated polyamines contribute to the observed impairment of leaf maturation.

Keywords:  ethylene; inhibition of biosynthesis; maturation; nic1/nic2 mutation; nicotine; ornithine decarboxylase; senescence

DOI:  https://doi.org/10.1002/pld3.77
J Chromatogr A. 2019 Jun 12. pii: S0021-9673(19)30636-3. [Epub ahead of print]

Simultaneous determination of eight underivatized biogenic amines in salted mackerel fillet by ion-pair solid-phase extraction and volatile ion-pair reversed-phase liquid chromatography-tandem mass spectrometry.

Naoki Ochi.

  A simple and accurate method was developed for the quantitative determination of eight biogenic amines (cadaverine, histamine, 2-phenylethylamine, putrescine, spermidine, spermine, tryptamine, and tyramine) in salted mackerel fillet. The eight biogenic amines in the samples were extracted with 5% trichloroacetic acid and then purified by ion-pair solid-phase extraction using a C18 cartridge and nonafluoropentanoic acid as the volatile ion-pair reagent, without the need for both derivatization and pH adjustment. Subsequently, the eight underivatized biogenic amines were separated and quantified by volatile ion-pair reversed-phase LC-MS/MS using a C18 column with the same volatile ion-pair reagent. The developed method was validated and showed good accuracy with mean recoveries of all the eight analytes in the range of 87-118% at two fortification levels (2.5 and 5 mg/kg). Finally, the proposed method was applied to the analysis of the eight biogenic amines in salted mackerel fillet samples.

Keywords:  Biogenic amines; Ion-pair liquid chromatography; Ion-pair solid-phase extraction; LC–MS/MS

DOI:  https://doi.org/10.1016/j.chroma.2019.06.027
Biomolecules. 2019 Jun 22. pii: E243. [Epub ahead of print]9(6):

Important Metabolites in Maintaining Folate Cycle, Homocysteine, and Polyamine Metabolism Associated with Ranibizumab Treatment in Cultured Human Tenon's Fibroblasts.

Siti Munirah Md Noh, Siti Hamimah Sheikh Abdul Kadir, Sushil Vasudevan.

  The anti-fibrotic properties of ranibizumab have been well documented. As an antagonist to vascular endothelial growth factor (VEGF), ranibizumab works by binding and neutralizing all active VEGF-A, thus limiting progressive cell growth and proliferation. Ranibizumab application in ocular diseases has shown remarkable desired effects; however, to date, its antifibrotic mechanism is not well understood. In this study, we identified metabolic changes in ranibizumab-treated human Tenon's fibroblasts (HTFs). Cultured HTFs were treated for 48 h with 0.5 mg/mL of ranibizumab and 0.5 mg/mL control IgG antibody which serves as a negative control. Samples from each group were injected into Agilent 6520 Q-TOF liquid chromatography/mass spectrometer (LC/MS) system to establish the metabolite expression in both ranibizumab treated cells and control group. Data obtained was analyzed using Agilent Mass Hunter Qualitative Analysis software to identify the most regulated metabolite following ranibizumab treatment. At p-value < 0.01 with the cut off value of two-fold change, 31 identified metabolites were found to be significantly upregulated in ranibizumab-treated group, with six of the mostly upregulated having insignificant role in fibroblast cell cycle and wound healing regulations. Meanwhile, 121 identified metabolites that were downregulated, and seven of the mostly downregulated are significantly involved in cell cycle and proliferation. Our findings suggest that ranibizumab abrogates the tissue scarring and wound healing process by regulating the expression of metabolites associated with fibrotic activity. In particular, we found that vitamin Bs are important in maintaining normal folate cycle, nucleotide synthesis, and homocysteine and spermidine metabolism. This study provides an insight into ranibizumab's mechanism of action in HTFs from the perspective of metabolomics.

Keywords:  anti-VEGF; ranibizumab; trabeculectomy

DOI:  https://doi.org/10.3390/biom9060243
Front Plant Sci. 2019 ;10 663

Conservation of Thermospermine Synthase Activity in Vascular and Non-vascular Plants.

Anna Solé-Gil, Jorge Hernández-García, María Pilar López-Gresa, Miguel A Blázquez, Javier Agustí.

  In plants, the only confirmed function for thermospermine is regulating xylem cells maturation. However, genes putatively encoding thermospermine synthases have been identified in the genomes of both vascular and non-vascular plants. Here, we verify the activity of the thermospermine synthase genes and the presence of thermospermine in vascular and non-vascular land plants as well as in the aquatic plant Chlamydomonas reinhardtii. In addition, we provide information about differential content of thermospermine in diverse organs at different developmental stages in some vascular species that suggest that, although the major role of thermospermine in vascular plants is likely to be xylem development, other potential roles in development and/or responses to stress conditions could be associated to such polyamine. In summary, our results in vascular and non-vascular species indicate that the capacity to synthesize thermospermine is conserved throughout the entire plant kingdom.

Keywords:  development; evolution; plants; polyamines; thermospermine

DOI:  https://doi.org/10.3389/fpls.2019.00663
Plants (Basel). 2019 Jun 21. pii: E184. [Epub ahead of print]8(6):

Polyamine Oxidases Play Various Roles in Plant Development and Abiotic Stress Tolerance.

Zhen Yu, Dongyu Jia, Taibo Liu.

  Polyamines not only play roles in plant growth and development, but also adapt to environmental stresses. Polyamines can be oxidized by copper-containing diamine oxidases (CuAOs) and flavin-containing polyamine oxidases (PAOs). Two types of PAOs exist in the plant kingdom; one type catalyzes the back conversion (BC-type) pathway and the other catalyzes the terminal catabolism (TC-type) pathway. The catabolic features and biological functions of plant PAOs have been investigated in various plants in the past years. In this review, we focus on the advance of PAO studies in rice, Arabidopsis, and tomato, and other plant species.

Keywords:  back conversion pathway; polyamine catabolism; polyamine oxidase; polyamines; stress response; terminal catabolism pathway

DOI:  https://doi.org/10.3390/plants8060184
J Membr Biol. 2019 Jun 25.

Function and Regulation of Acid Resistance Antiporters.

Eva-Maria Krammer, Martine Prévost.

  Bacterial pathogens are a major cause of foodborne diseases and food poisoning. To cope with the acid conditions encountered in different environments such as in fermented food or in the gastric compartment, neutralophilic bacteria have developed several adaptive mechanisms. One of those mechanisms, the amino acid dependent system, consumes intracellular protons in biochemical reactions. It involves an antiporter that facilitates the exchange of external substrate amino acid for internal product and a cytoplasmic decarboxylase that catalyzes a proton-consuming decarboxylation of the substrate. So far, four acid resistance antiporters have been discovered, namely the glutamate-γ-aminobutyric acid antiporter GadC, the arginine-agmatine antiporter AdiC, the lysine-cadaverine antiporter CadB, and the ornithine-putrescine antiporter PotE. The 3D structures of AdiC and GadC, reveal an inverted-repeat fold of two times 5 transmembrane helices, typical of the amino acid-polyamine-organocation (APC) superfamily of transporters. This review summarizes our current knowledge on the transport mechanism, the pH regulation and the selectivity of these four acid resistance antiporters. It also highlights that AdiC is a paradigm for eukaryotic amino acid transporters of the APC superfamily as structural models of several of these transporters built using AdiC structures were exploited to unveil their mechanisms of amino acid recognition and translocation.

Keywords:  APC transporter; Acid resistance; Foodborne disease; Molecular simulation; Transport mechanism; pH regulation

DOI:  https://doi.org/10.1007/s00232-019-00073-6