bims-polyam 2021-07-11 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–07–11
eight papers selected by
Sebastian J. Hofer, University of Graz

Polyamine metabolism is a central determinant of helper T cell lineage fidelity.
The metabolic role of spermidine in obesity: Evidence from cells to community.
A link between urease and polyamine metabolism in Cryptococcus neoformans.
Expression profile of seven polyamine oxidase genes in rice (Oryza sativa) in response to abiotic stresses, phytohormones and polyamines.
Stem canker caused by Phomopsis spp. Induces changes in polyamine levels and chlorophyll fluorescence parameters in pecan leaves.
High-throughput screening of salivary polyamine markers for discrimination of colorectal cancer by multisegment injection capillary electrophoresis tandem mass spectrometry.
Metabolic modeling of single Th17 cells reveals regulators of autoimmunity.
Metabolome-Microbiome Responses of Growing Pigs Induced by Time-Restricted Feeding.

Cell. 2021 Jun 25. pii: S0092-8674(21)00708-X. [Epub ahead of print]

Polyamine metabolism is a central determinant of helper T cell lineage fidelity.

Daniel J Puleston, Francesc Baixauli, David E Sanin, Joy Edwards-Hicks, Matteo Villa, Agnieszka M Kabat, Marcin M Kamiński, Michal Stanckzak, Hauke J Weiss, Katarzyna M Grzes, Klara Piletic, Cameron S Field, Mauro Corrado, Fabian Haessler, Chao Wang, Yaarub Musa, Lena Schimmelpfennig, Lea Flachsmann, Gerhard Mittler, Nir Yosef, Vijay K Kuchroo, Joerg M Buescher, Stefan Balabanov, Edward J Pearce, Douglas R Green, Erika L Pearce.

  Polyamine synthesis represents one of the most profound metabolic changes during T cell activation, but the biological implications of this are scarcely known. Here, we show that polyamine metabolism is a fundamental process governing the ability of CD4+ helper T cells (TH) to polarize into different functional fates. Deficiency in ornithine decarboxylase, a crucial enzyme for polyamine synthesis, results in a severe failure of CD4+ T cells to adopt correct subset specification, underscored by ectopic expression of multiple cytokines and lineage-defining transcription factors across TH cell subsets. Polyamines control TH differentiation by providing substrates for deoxyhypusine synthase, which synthesizes the amino acid hypusine, and mice in which T cells are deficient for hypusine develop severe intestinal inflammatory disease. Polyamine-hypusine deficiency caused widespread epigenetic remodeling driven by alterations in histone acetylation and a re-wired tricarboxylic acid (TCA) cycle. Thus, polyamine metabolism is critical for maintaining the epigenome to focus TH cell subset fidelity.

Keywords:  T cells; eIF5A; hypusine; immunity; immunometabolism; metabolism; polyamines

DOI:  https://doi.org/10.1016/j.cell.2021.06.007
Obes Res Clin Pract. 2021 Jul 01. pii: S1871-403X(21)00095-8. [Epub ahead of print]

The metabolic role of spermidine in obesity: Evidence from cells to community.

Yanee Choksomngam, Sintip Pattanakuhar, Nipon Chattipakorn, Siriporn C Chattipakorn.

  Spermidine is a natural polyamine existing in all living cells known to play an important role in cellular functions. Recently, several studies have reported the effect of alterations in the spermidine pool on metabolic pathways. It has been shown that activation of spermidine/spermine N-1-acetyl-transferase (SSAT), the rate-limiting enzyme in polyamine catabolism, improved glucose and lipid metabolism. In addition, spermidine supplementation has been shown to protect against diet-induced obesity in animal models. However, some clinical studies demonstrated that polyamine levels are increased in childhood obesity and metabolic syndrome patients with type 2 diabetes (T2DM), while polyamine-rich food is associated with a lower incidence of cardiovascular disease (CVD). Therefore, this review aims to summarize and discuss the evidence from in vitro, in vivo and clinical studies on the possible roles of spermidine on metabolic pathways under physiological and obese conditions. All consistent and inconsistent findings are discussed and further studies aiming to fill any gaps in the knowledge are proposed.

Keywords:  Metabolic pathways; Obesity; Polyamine; Spermidine

DOI:  https://doi.org/10.1016/j.orcp.2021.06.009
Microb Pathog. 2021 Jul 01. pii: S0882-4010(21)00348-X. [Epub ahead of print]158 105076

A link between urease and polyamine metabolism in Cryptococcus neoformans.

Barbra Toplis, Caylin Bosch, Marietjie Stander, Malcolm Taylor, John R Perfect, Alfred Botha.

  The urease enzyme of Cryptococcus neoformans is linked to different metabolic pathways within the yeast cell, several of which are involved in polyamine metabolism. Cryptococcal biogenic amine production is, however, largely unexplored and is yet to be investigated in relation to urease. The aim of this study was therefore to explore and compare polyamine metabolism in wild-type, urease-negative and urease-reconstituted strains of C. neoformans. Mass spectrometry analysis showed that agmatine and spermidine were the major extra- and intracellular polyamines of C. neoformans and significant differences were observed between 26 and 37 °C. In addition, compared to the wild-type, the relative percentages of extracellular putrescine and spermidine were found to be lower and agmatine higher in cultures of the urease-deficient mutant. The inverse was true for intracellular spermidine and agmatine. Cyclohexylamine was a more potent polyamine inhibitor compared to DL-α-difluoromethylornithine and inhibitory effects were more pronounced at 37 °C than at 26 °C. At both temperatures, the urease-deficient mutant was less susceptible to cyclohexylamine treatment compared to the wild-type. For both inhibitors, growth inhibition was alleviated with polyamine supplementation. This study has provided novel insight into the polyamine metabolism of C. neoformans, highlighting the involvement of urease in biogenic amine production.

Keywords:  Cryptococcus; Polyamine biosynthesis; Urease; Virulence factor; Yeast metabolism

DOI:  https://doi.org/10.1016/j.micpath.2021.105076
Physiol Mol Biol Plants. 2021 Jun;27(6): 1353-1359

Expression profile of seven polyamine oxidase genes in rice (Oryza sativa) in response to abiotic stresses, phytohormones and polyamines.

G H M Sagor, Masataka Inoue, Tomonobu Kusano, Thomas Berberich.

  Polyamine levels are controlled by biosynthesis, intra- and inter-cellular flux by the respective transporters, and catabolism. The catabolism is catalyzed by two groups of enzymes. One is copper-containing amine oxidases and the other is polyamine oxidases (PAOs). In Oryza sativa, seven PAO genes exist and they are termed as OsPAO1 to OsPAO7. However, their physiological function has not been elucidated yet. Here, we examined the expressional changes of seven OsPAO genes upon abiotic and oxidative stress, phytohormone, and exogenous polyamines application. The transcript of extracellular polyamine oxidase OsPAO2 and OsPAO6 are strongly induced upon wounding, drought, salinity, oxidative stress (H2O2), and exogenous application of jasmonic acid, spermidine, spermine, thermospermine and negatively regulated upon indole acetic acid, isopentenyl adenine (iPT), gibberellic acid (GA), abscisic acid; OsPAO7 is to iPT, GA and all polyamines; OsPAO4 and OsPAO5 are mildly responsive to heat, cold, oxidative stress. These results suggest that polyamine oxidase encoding extracellular enzyme may play a pivotal role during exogenous stimulus to protect the plant cell.
Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-021-01006-1.

Keywords:  Abiotic stress; Hormone response; Oryza sativa; Polyamine; Polyamine oxidase

DOI:  https://doi.org/10.1007/s12298-021-01006-1
Plant Physiol Biochem. 2021 Jun 29. pii: S0981-9428(21)00363-6. [Epub ahead of print]166 761-769

Stem canker caused by Phomopsis spp. Induces changes in polyamine levels and chlorophyll fluorescence parameters in pecan leaves.

Guillermo Martin Mantz, Franco Ruben Rossi, Pablo Esteban Viretto, María Cristina Noelting, Santiago Javier Maiale.

  Pecan plants are attacked by the fungus Phomopsis spp. that causes stem canker, a serious and emerging disease in commercial orchards. Stem canker, which has been reported in several countries, negatively affects tree canopy health, eventually leading to production losses. The purpose of this study was to inquire into the physiology of pecan plants under stem canker attack by Phomopsis spp. To this end, pecan plants were inoculated with an isolate of Phomopsis spp. and several parameters, such as polyamines, proline, sugars, starch, chlorophyll fluorescence and canopy temperature were analysed. Under artificial inoculation, a high disease incidence was observed with symptoms similar to those in plants showing stem canker under field conditions. Furthermore, the infected stem showed dead tissue with brown necrotic discolouration in the xylem tissue. The free polyamines putrescine, spermidine, and spermine were detected and their levels decreased as leaves aged in the infected plants with respect to the controls. Chlorophyll fluorescence parameters, such as Sm, ψEO, and QbRC decreased under plant infection and therefore the K-band increased. Canopy temperature and proline content increased in the infected plants with respect to the controls while sugar content decreased. These data suggest that stem canker caused by Phomopsis spp. induces physiological changes that are similar to those observed in plants under drought stress. To our knowledge, this is the first study that documents the physiological and biochemical effects derived from pecan-Phomopsis interaction.

Keywords:  Chlorophyll fluorescence; Pecan; Phomopsis; Polyamines; Proline

DOI:  https://doi.org/10.1016/j.plaphy.2021.06.050
J Chromatogr A. 2021 Jun 20. pii: S0021-9673(21)00479-9. [Epub ahead of print]1652 462355

High-throughput screening of salivary polyamine markers for discrimination of colorectal cancer by multisegment injection capillary electrophoresis tandem mass spectrometry.

Kaori Igarashi, Sana Ota, Miku Kaneko, Akiyoshi Hirayama, Masanobu Enomoto, Kenji Katumata, Masahiro Sugimoto, Tomoyoshi Soga.

  Polyamine metabolites provide pathophysiological information on disease or therapeutic efficacy, yet rapid screening methods for these biomarkers are lacking. Here, we developed high-throughput polyamine metabolite profiling based on multisegment injection capillary electrophoresis triple quadrupole tandem mass spectrometry (MSI-CE-MS/MS), which allows sequential 40-sample injection followed by electrophoretic separation and specific mass detection. To achieve consecutive analysis of polyamine samples, 1 M formic acid was used as the background electrolyte (BGE). The BGE spacer volume had an apparent effect on peak resolution among samples, and 20 nL was selected as the optimal volume. The use of polyamine isotopomers as the internal standard enabled the correction of matrix effects in MS detection. This method is sensitive, selective and quantitative, and its utility was demonstrated by screening polyamines in 359 salivary samples within 360 min, resulting in discrimination of colorectal cancer patients from noncancer controls.

Keywords:  Biomarker; Colorectal cancer; Mass spectrometry; Multisegment injection; Polyamine; Saliva; capillary electrophoresis

DOI:  https://doi.org/10.1016/j.chroma.2021.462355
Cell. 2021 Jun 29. pii: S0092-8674(21)00700-5. [Epub ahead of print]

Metabolic modeling of single Th17 cells reveals regulators of autoimmunity.

Allon Wagner, Chao Wang, Johannes Fessler, David DeTomaso, Julian Avila-Pacheco, James Kaminski, Sarah Zaghouani, Elena Christian, Pratiksha Thakore, Brandon Schellhaass, Elliot Akama-Garren, Kerry Pierce, Vasundhara Singh, Noga Ron-Harel, Vivian Paraskevi Douglas, Lloyd Bod, Alexandra Schnell, Daniel Puleston, Raymond A Sobel, Marcia Haigis, Erika L Pearce, Manoocher Soleimani, Clary Clish, Aviv Regev, Vijay K Kuchroo, Nir Yosef.

  Metabolism is a major regulator of immune cell function, but it remains difficult to study the metabolic status of individual cells. Here, we present Compass, an algorithm to characterize cellular metabolic states based on single-cell RNA sequencing and flux balance analysis. We applied Compass to associate metabolic states with T helper 17 (Th17) functional variability (pathogenic potential) and recovered a metabolic switch between glycolysis and fatty acid oxidation, akin to known Th17/regulatory T cell (Treg) differences, which we validated by metabolic assays. Compass also predicted that Th17 pathogenicity was associated with arginine and downstream polyamine metabolism. Indeed, polyamine-related enzyme expression was enhanced in pathogenic Th17 and suppressed in Treg cells. Chemical and genetic perturbation of polyamine metabolism inhibited Th17 cytokines, promoted Foxp3 expression, and remodeled the transcriptome and epigenome of Th17 cells toward a Treg-like state. In vivo perturbations of the polyamine pathway altered the phenotype of encephalitogenic T cells and attenuated tissue inflammation in CNS autoimmunity.

Keywords:  DFMO; T helper 17 cell; experimental autoimmune encephalomyelitis; immunometabolism; in silico metabolic modeling; multiple sclerosis; polyamines; putrescine; single cell transcriptomics; spermidine

DOI:  https://doi.org/10.1016/j.cell.2021.05.045
Front Vet Sci. 2021 ;8 681202

Metabolome-Microbiome Responses of Growing Pigs Induced by Time-Restricted Feeding.

Hongyu Wang, Pengke Xia, Zhiyang Lu, Yong Su, Weiyun Zhu.

  Time-restricted feeding (TRF) mode is a potential strategy in improving the health and production of farm animals. However, the effect of TRF on microbiota and their metabolism in the large intestine of the host remains unclear. Therefore, the present study aimed to investigate the responses of microbiome and metabolome induced by TRF based on a growing-pig model. Twelve crossbred growing barrows were randomly allotted into two groups with six replicates (1 pig/pen), namely, the free-access feeding group (FA) and TRF group. Pigs in the FA group were fed free access while the TRF group were fed free access within a regular time three times per day at 07:00-08:00, 12:00-13:00, and 18:00-19:00, respectively. Results showed that the concentrations of NH4-N, putrescine, cadaverine, spermidine, spermine, total biogenic amines, isobutyrate, butyrate, isovalerate, total SCFA, and lactate were increased while the pH value in the colonic digesta and the concentration of acetate was decreased in the TRF group. The Shannon index was significantly increased in the TRF group; however, no significant effects were found in the Fisher index, Simpson index, ACE index, Chao1 index, and observed species between the two groups. In the TRF group, the relative abundances of Prevotella 1 and Eubacterium ruminantium group were significantly increased while the relative abundances of Clostridium sensu sticto 1, Lactobacillus, and Eubacterium coprostanoligenes group were decreased compared with the FA group. PLS-DA analysis revealed an obvious and regular variation between the FA and TRF groups, further pathway enrichment analysis showed that these differential features were mainly enriched in pyrimidine metabolism, nicotinate and nicotinamide metabolism, glycerolipid metabolism, and fructose and mannose metabolism. In addition, Pearson's correlation analysis indicated that the changes in the microbial genera were correlated with the colonic metabolites. In conclusion, these results together indicated that although the overall microbial composition in the colon was not changed, TRF induced the gradient changes of the nutrients and metabolites which were correlated with certain microbial genera including Lactobacillus, Eubacterium_ruminantium group, Eubacterium coprostanoligenes group, Prevotella 1, and Clostridium sensu sticto 1. However, more studies are needed to understand the impacts of TRF on the health and metabolism of growing pigs.

Keywords:  growing pigs; metabolome; microbial metabolites; microbiome; time-restricted feeding

DOI:  https://doi.org/10.3389/fvets.2021.681202