bims-polyam 2021-04-11 papers

Issue of 2021–04–11
six papers selected by
Sebastian J. Hofer, University of Graz

Nat Commun. 2021 04 08. 12(1): 2105

Symbiotic polyamine metabolism regulates epithelial proliferation and macrophage differentiation in the colon.

Atsuo Nakamura, Shin Kurihara, Daisuke Takahashi, Wakana Ohashi, Yutaka Nakamura, Shunsuke Kimura, Masayoshi Onuki, Aiko Kume, Yukiko Sasazawa, Yukihiro Furusawa, Yuuki Obata, Shinji Fukuda, Shinji Saiki, Mitsuharu Matsumoto, Koji Hase.

Intestinal microbiota-derived metabolites have biological importance for the host. Polyamines, such as putrescine and spermidine, are produced by the intestinal microbiota and regulate multiple biological processes. Increased colonic luminal polyamines promote longevity in mice. However, no direct evidence has shown that microbial polyamines are incorporated into host cells to regulate cellular responses. Here, we show that microbial polyamines reinforce colonic epithelial proliferation and regulate macrophage differentiation. Colonisation by wild-type, but not polyamine biosynthesis-deficient, Escherichia coli in germ-free mice raises intracellular polyamine levels in colonocytes, accelerating epithelial renewal. Commensal bacterium-derived putrescine increases the abundance of anti-inflammatory macrophages in the colon. The bacterial polyamines ameliorate symptoms of dextran sulfate sodium-induced colitis in mice. These effects mainly result from enhanced hypusination of eukaryotic initiation translation factor. We conclude that bacterial putrescine functions as a substrate for symbiotic metabolism and is further absorbed and metabolised by the host, thus helping maintain mucosal homoeostasis in the intestine.

DOI: https://doi.org/10.1038/s41467-021-22212-1

Open Life Sci. 2021 ;16(1): 39-45

Exogenous spermidine affects polyamine metabolism in the mouse hypothalamus.

Dongmei Jiang, Guilin Mo, Yilong Jiang, Bo Kang.

Spermidine is important for the hypothalamic control of pituitary secretion of hormones involved in neuroendocrine functions in mammals. In this study, the effect of exogenous spermidine on the expression of genes and proteins related to polyamine metabolism and polyamine levels was examined. The results indicated that treatment with spermidine at 0.05 mg/g (BW) significantly increased the levels of Oaz1 mRNA and protein expression and decreased putrescine content in mouse hypothalamus (p < 0.05). The administration with spermidine at 0.10 mg/g significantly increased the levels of Oaz1, Oaz2, and Odc expression in mouse hypothalamus (p < 0.05). Treatment with spermidine at 0.05 mg/g significantly increased the levels of Ssat mRNA expression and reduced the level of Smo mRNA expression in mouse hypothalamus (p < 0.05). Putrescine concentrations in the hypothalamus after the administration of spermidine at 0.10 and 0.15 mg/g were significantly higher than those in the control group (p < 0.05). The concentration of both spermidine and spermine in the hypothalamus after the administration of spermidine at 0.15 mg/g was decreased significantly (p < 0.05). In summary, our results indicate that exogenous spermidine affects polyamine homeostasis in the mouse hypothalamus by modulating the expression of genes and proteins related to polyamine metabolism.

Keywords: hypothalamus; polyamine metabolism; putrescine; spermidine; spermine

DOI: https://doi.org/10.1515/biol-2021-0006

Aging (Albany NY). 2021 Apr 03. 13

Alzheimer's disease as a chronic maladaptive polyamine stress response.

Baruh Polis, David Karasik, Abraham O Samson.

Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by an evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by upsurge in polyamines levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer's disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia.

Keywords: aging; arginase; neurodegeneration; polyamines; senescence

DOI: https://doi.org/10.18632/aging.202928

Protein Sci. 2021 Apr 07.

Criticality of a conserved tyrosine residue in the SpeG protein from Escherichia coli.

Van Thi Bich Le, Joseph Dang, Ee Qi Lim, Misty L Kuhn.

The SpeG spermidine/spermine N-acetyltransferase (SSAT) from Escherichia coli belongs to the Gcn5-related N-acetyltransferase (GNAT) superfamily of proteins. In vitro characterization of this enzyme shows it acetylates the polyamines spermine and spermidine, with a preference toward spermine. This enzyme has a conserved tyrosine residue (Y135) that is found in all SSAT proteins and many GNAT functional subfamilies. It is located near acetyl coenzyme A in the active center of these proteins and has been suggested to act as a general acid in a general acid/base chemical mechanism. In contrast, a previous study showed this residue was not critical for E. coli SpeG enzymatic activity when mutated to phenylalanine. This result was quite different from previous studies with a comparable residue in the human and mouse SSAT proteins, which also acetylate spermine and spermidine. Therefore, we constructed several mutants of the E. coli SpeG Y135 residue and tested their enzymatic activity. We found this conserved residue was indeed critical for E. coli SpeG enzyme activity and may behave similarly in other SSAT proteins. This article is protected by copyright. All rights reserved.

Keywords: Gcn5-related N-acetyltransferase; SpeG; general acid; polyamine; spermidine/spermine N-acetyltransferase

DOI: https://doi.org/10.1002/pro.4078

Plant Physiol Biochem. 2021 Mar 23. pii: S0981-9428(21)00150-9. [Epub ahead of print]163 55-67

Chitosan and putrescine modulate reactive oxygen species metabolism and physiological responses during chili fruit ripening.

Arijit Ghosh, Indraneel Saha, Subhas Chandra Debnath, Mirza Hasanuzzaman, Malay Kumar Adak.

We investigated the combined effect of chitosan (CHT) and putrescine (PUT) on the postharvest shelf life of Capsicum fruit concerning the metabolism of reactive oxygen species (ROS) through direct and indirect effects on ripening characters cell wall hydrolyzing enzyme and ROS metabolism. The PUT and CHT directly affected quality indices like color, firmness and water loss with a concomitant oxidative bust in the development of O2•- and H2O2 in fruit pulp. This was accompanied by significant suppression of respiratory flux, a decrease of total soluble solids and ascorbic acid content throughout postharvest storage. PUT applied with CHT modified the oxidative metabolism of fruits by a significant reduction in the level of O2•- and H2O2 content. In addition, a significant accumulation of total polyamine under respective treatment was reasonably correlated with both ROS producing enzyme as well as H2O2 and O2•-. Wall hydrolyzing enzymes like pectin methyl esterase and cellulase had marked downregulation both under PUT and CHT + PUT treatment. Moreover, on close observation, the combinational effects of PUT and CHT had better effects in the regulation of those enzymes as compared to individual treatment. Fruits restore higher antioxidative capacities as evident with superoxide dismutase (SOD), guaiacol peroxidases (GPX), ascorbate peroxidase (APX) catalase (CAT), glutathione peroxidase (GPX), NADPH oxidase (NOX) and glutathione reductase (GR), indicating their roles on fruit coat softening. Finally, the treatment of PUT and CHT in combination increased shelf life vis-à-vis the quality of fruit.

Keywords: Antioxidant defense; Biostimulants; Capsicum; Cell wall hydrolyzing enzymes; Polyamines; Postharvest quality

DOI: https://doi.org/10.1016/j.plaphy.2021.03.026

J Anim Sci Biotechnol. 2021 Apr 08. 12(1): 46

Pre-implantation exogenous progesterone and pregnancy in sheep. II. Effects on fetal-placental development and nutrient transporters in late pregnancy.

Katherine M Halloran, Emily C Hoskins, Claire Stenhouse, Robyn M Moses, Kathrin A Dunlap, M Carey Satterfield, Heewon Seo, Gregory A Johnson, Guoyao Wu, Fuller W Bazer.

BACKGROUND: Administration of progesterone (P4) to ewes during the first 9 to 12 days of pregnancy accelerates blastocyst development by day 12 of pregnancy, likely due to P4-induced up-regulation of key genes in uterine epithelia responsible for secretion and transport of components of histotroph into the uterine lumen. This study determined if acceleration of blastocyst development induced by exogenous P4 during the pre-implantation period affects fetal-placental development on day 125 of pregnancy. Suffolk ewes (n = 35) were mated to fertile rams and assigned randomly to receive daily intramuscular injections of either corn oil vehicle (CO, n = 18) or 25 mg progesterone in CO (P4, n = 17) for the first 8 days of pregnancy. All ewes were hysterectomized on day 125 of pregnancy and: 1) fetal and placental weights and measurements were recorded; 2) endometrial and placental tissues were analyzed for the expression of candidate mRNAs involved in nutrient transport and arginine metabolism; and 3) maternal plasma, fetal plasma, allantoic fluid, and amniotic fluid were analyzed for amino acids, agmatine, polyamines, glucose, and fructose.
RESULTS: Treatment of ewes with exogenous P4 did not alter fetal or placental growth, but increased amounts of aspartate and arginine in allantoic fluid and amniotic fluid, respectively. Ewes that received exogenous P4 had greater expression of mRNAs for SLC7A1, SLC7A2, SLC2A1, AGMAT, and ODC1 in endometria, as well as SLC1A4, SLC2A5, SLC2A8 and ODC1 in placentomes. In addition, AZIN2 protein was immunolocalized to uterine luminal and glandular epithelia in P4-treated ewes, whereas AZIN2 localized only to uterine luminal epithelia in CO-treated ewes.
CONCLUSIONS: This study revealed that exogenous P4 administered in early pregnancy influenced expression of selected genes for nutrient transporters and the expression of a protein involved in polyamine synthesis on day 125 of pregnancy, suggesting a 'programming' effect of P4 on gene expression that affected the composition of nutrients in fetal-placental fluids.

Keywords: Amino acids; Endometrium; Fructose; Gene expression; Glucose; Placenta; Polyamines; Progesterone

DOI: https://doi.org/10.1186/s40104-021-00567-1