bims-polyam 2020-11-01 papers

on Polyamines

Issue of 2020–11–01
nine papers selected by
Sebastian J. Hofer, University of Graz and Alexander Ivanov, Engelhardt Institute of Molecular Biology

Spermidine is not an Independent Factor Regulating Limb Muscle Mass in Mice following Androgen Deprivation.
Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy.
Evidences for Agmatine alterations in Aβ1-42induced Memory Impairment in Mice.
LINC00265 targets miR-382-5p to regulate SAT1, VAV3 and angiogenesis in osteosarcoma.
Serum Spermidine as a Novel Potential Predictor for Fragility Fractures.
Adaptability to abiotic stress regulated by γ-aminobutyric acid in relation to alterations of endogenous polyamines and organic metabolites in creeping bentgrass.
DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines.
Physiological and transcriptome changes induced by exogenous putrescine in anthurium under chilling stress.
Voluntary activity reverses spermidine-induced myocardial fibrosis and lipid accumulation in the obese male mouse.

Appl Physiol Nutr Metab. 2020 Oct 30.

Spermidine is not an Independent Factor Regulating Limb Muscle Mass in Mice following Androgen Deprivation.

Bradley S Gordon, Michael L Rossetti, Robert A Casero.

Maintaining a critical amount of skeletal muscle mass is linked to reduced morbidity and mortality. In males, testicular androgens regulate muscle mass with a loss of androgens being critical as it is associated with muscle atrophy. Atrophy of the limb muscles is particularly important, but the pathways by which androgens regulate limb muscle mass remain equivocal. We used microarray analysis to identify changes to genes involved with polyamine metabolism in the tibialis anterior (TA) muscle of castrated mice. Of the polyamines, the concentration of spermidine (SPD) was significantly reduced in the TA of castrated mice. To assess whether SPD was an independent factor by which androgens regulate limb muscle mass, we treated castrated mice with SPD for 8 weeks and compared them to sham operated mice. Though this treatment paradigm effectively restored SPD concentrations in the TA muscles of castrated mice, mass of the limb muscles (i.e. TA, gastrocnemius, plantaris, and soleus) were not increased to the levels observed in sham animals. Consistent with those findings, muscle force production was also not increased by SPD treatment. Overall, these data demonstrate for the first time that SPD is not an independent factor by which androgens regulate limb skeletal muscle mass. NOVELTY BULLETS -Polyamines regulate growth in various cells/tissues -Spermidine concentrations are reduced in the limb skeletal muscle following androgen depletion -Restoring Spermidine concentrations in the limb skeletal muscle does not increase limb muscle mass or force production.

DOI: https://doi.org/10.1139/apnm-2020-0404
Free Radic Biol Med. 2020 Oct 24. pii: S0891-5849(20)31303-4. [Epub ahead of print]

Spermidine endows macrophages anti-inflammatory properties by inducing mitochondrial superoxide-dependent AMPK activation, Hif-1α upregulation and autophagy.

Rui Liu, Xiaolei Li, Hui Ma, Qian Yang, Qianwen Shang, Lin Song, Zhiyuan Zheng, Shengchao Zhang, Yongsha Pan, Peiqing Huang, Jiankai Fang, Yanan Li, Zhanhong Liu, Lijuan Cao, Chao Feng, Zheng Gong, Yongjing Chen, Ying Wang, Gerry Melino, Changshun Shao, Yufang Shi.

  Distinct metabolic programs, either energy-consuming anabolism or energy-generating catabolism, were required for different biological functions. Macrophages can adopt different immune phenotypes in response to various cues and exhibit anti- or pro-inflammatory properties relying on catabolic pathways associated with oxidative phosphorylation (OXPHOS) or glycolysis. Spermidine, a natural polyamine, has been reported to regulate inflammation through inducing anti-inflammatory (M2) macrophages. However, the underlying mechanisms remain elusive. We show here that the M2-polarization induced by spermidine is mediated by mitochondrial reactive oxygen species (mtROS). The levels of mitochondrial superoxide and H2O2 were markedly elevated by spermidine. Mechanistically, mtROS were found to activate AMP-activated protein kinase (AMPK), which in turn enhanced mitochondrial function. Furthermore, hypoxia-inducible factor-1α (Hif-1α) was upregulated by the AMPK activation and mtROS and was required for the expression of anti-inflammatory genes and induction of autophagy. Consistent with previous report that autophagy is required for the M2 polarization, we found that the M2 polarization induced by spermidine was also mediated by increased autophagy. The macrophages treated with spermidine in vitro were found to ameliorate Dextran Sulfate Sodium (DSS)-induced inflammatory bowel disease (IBD) in mice. Thus, spermidine can elicit an anti-inflammatory program driven by mtROS-dependent AMPK activation, Hif-1α stabilization and autophagy induction in macrophages. Our studies revealed a critical role of mtROS in shaping macrophages into M2-like phenotype and provided novel information for management of inflammatory disease by spermidine.

Keywords:  AMPK; M2 polarization; autophagy; hypoxia-inducible factor-1α; mitochondrial ROS; spermidine

DOI:  https://doi.org/10.1016/j.freeradbiomed.2020.10.029
Neurosci Lett. 2020 Oct 27. pii: S0304-3940(20)30717-5. [Epub ahead of print] 135447

Evidences for Agmatine alterations in Aβ1-42induced Memory Impairment in Mice.

Madhura P Dixit, Shubham N Rahmatkar, Prachi Raut, Milind J Umekar, Brijesh G Taksande, Nandkishor R Kotagale.

  Alzheimer's disease is an age related progressive neurodegenerative disorder characterized by decline in cognitive functions, such as memory loss and behavioural abnormalities. The present study sought to assess alterations in agmatine metabolism in the beta-amyloid (Aβ1-42) Alzheimer's disease mouse model. Aβ1-42 injected mice showed impairment of cognitive functioning as evidenced by increased working and reference memory errors in radial arm maze (RAM). This cognitive impairment was associated with a reduction in theagmatine levels and elevation in its degrading enzyme, agmatinase, whereas reduced immunocontent was observed in its synthesizing enzyme arginine decarboxylase expression within hippocampus and prefrontal cortex. Chronic agmatine treatment and its endogenous modulation by L-arginine, or arcaine or aminoguanidine prevented the learning and memory impairment induced by single intracranial Aβ1-42 peptide injection. In conclusion, the present study suggests the importance of the endogenous agmatinergic system in β-amyloid induced memory impairment in mice.

Keywords:  Agmatine; Alzheimer’s disease; Cognitive impairment; β-Amyloid

DOI:  https://doi.org/10.1016/j.neulet.2020.135447
Aging (Albany NY). 2020 Aug 14. 12

LINC00265 targets miR-382-5p to regulate SAT1, VAV3 and angiogenesis in osteosarcoma.

Ying Xiao, Chunling Li, Hongyue Wang, Yijun Liu.

  We explored the mechanism by which LINC00265 regulates angiogenesis of osteosarcoma cells via the miR-382-5p/spermidine/spermine N1-acetyltransferase-1 (SAT1) and miR-382-5p/vav guanine nucleotide exchange factor 3 (VAV3) axis. Cell scratch assay, Transwell assay and tube formation assay were applied to detect cell migration, invasion and tube formation abilities. The effects of LINC00265 targeting miR-382-5p in osteosarcoma in vivo were studied using a tumour-burden assay. A total of 70 genes potentially involved in osteosarcoma angiogenesis were identified, and a Gene Ontology (GO) analysis found that SAT1 and VAV3 were closely related to angiogenesis. Bioinformatics analysis and clinical experiments confirmed that LINC00265, SAT1 and VAV3 were overexpressed in osteosarcoma and related to a poor prognosis, whereas miR-382-5p was downregulated and associated with a poor prognosis. It was confirmed that LINC00265 promoted the proliferation, migration, invasion and angiogenesis of osteosarcoma cells by targeting miR-382-5p to mediate SAT1 and VAV3. Collectively, LINC00265 might promote proliferation, migration, invasion and angiogenesis by targeting miR-382-5p/SAT1 and miR-382-5p/VAV3 in osteosarcoma.

Keywords:  LINC00265; angiogenesis; miR-382-5p; spermidine/spermine N1-acetyltransferase-1; vasculogenic mimicry

DOI:  https://doi.org/10.18632/aging.103762
J Clin Endocrinol Metab. 2020 Oct 25. pii: dgaa745. [Epub ahead of print]

Serum Spermidine as a Novel Potential Predictor for Fragility Fractures.

Sung Hye Kong, Jung Hee Kim, Chan Soo Shin.

   CONTEXT: Metabolomics is an emerging tool that provides insights into the dynamics of phenotypic changes. It is a potential method for the discovery of novel serum markers of fracture.
OBJECTIVE: To identify metabolite parameters that can be used as a proxy for osteoporotic fracture risk.
DESIGN: Prospective study based on the Ansung cohort in Korea.
SETTING: The general community.
PARTICIPANTS: 1,504 participants with metabolomic analyses.
INTERVENTIONS: None.
MAIN OUTCOME MEASURE: Fragility fractures.
RESULTS: We measured 135 baseline metabolite profiles in fasting serum of the participants. The participants had a mean age of 60.2 years and comprised of 585 (38.9%) men. During a mean 9-year follow-up, 112 osteoporotic fracture events occurred. Of all metabolites measured, only serum spermidine concentrations were positively associated with the risk of fracture (hazard ratio [HR] per 1 μM of spermidine 1.35, 95% confidence interval [CI]= 1.03-1.65, p=0.020) after adjustments for age, sex, BMI, diabetes, hypertension, smoking status, previous fracture history, and baseline tibial quantitative ultrasound. Participants with spermidine concentrations >1.57 μM had a 2.2-fold higher risk of fractures (95% CI 1.08-4.51, p=0.030) compared to those with concentrations ≤1.57 μM after adjustment. In a subgroup analysis, women with baseline spermidine concentrations >1.57 μM also had a 2.4-fold higher risk of fracture than those with concentrations ≤1.57 μM (95% CI 1.02-5.48, p=0.047).
CONCLUSIONS: Increased baseline spermidine concentrations were associated with a risk of osteoporotic fracture during a mean 9-year follow-up. The biological significance of the metabolites in the musculoskeletal system could be a subject for future studies.

Keywords:  Fracture; Polyamine; Predictor; Prospective Cohort; Spermidine

DOI:  https://doi.org/10.1210/clinem/dgaa745
Plant Physiol Biochem. 2020 Oct 23. pii: S0981-9428(20)30527-1. [Epub ahead of print]157 185-194

Adaptability to abiotic stress regulated by γ-aminobutyric acid in relation to alterations of endogenous polyamines and organic metabolites in creeping bentgrass.

Zhou Li, Bizhen Cheng, Yan Peng, Yan Zhang.

  The frequency and severity of global abiotic stresses such as heat, drought, and salt stress are increasing due to climate changes. Objectives of this study were to investigate effects of γ-aminobutyric acid (GABA) priming on inducing plants' acclimation to abiotic stress associated with alterations of endogenous polyamines (PAs), amino acids, and sugars in creeping bentgrass (Agrostis stolonifera). The pretreatment with GABA fertigation significantly alleviated heat-, drought-, and salt-induced declines in leaf relative water content, chlorophyll content, cell membrane stability, photochemical efficiency (Fv/Fm), and performance index on absorption basis (PIABS), and also further decreased stress-caused decline in osmotic potential in leaves. The GABA priming uniformly increased total PAs, spermidine, amino acids involved in GABA shunt (GABA, glutamic acid, and alanine), and other amino acids (phenylalanine, aspartic acid, and glycine) accumulation under heat, drought, and salt stress. The GABA priming also significantly improved methionine content under heat and drought stress, maltose, galactose, and talose content under heat and salt stress, or cysteine, serine, and threonine content under drought and salt stress. Interestingly, the GABA priming uniquely led to significant accumulation of spermine, fructose, and glucose under heat stress, putrescine, proline, and mannose under drought stress, or arginine, trehalose and xylose under salt stress, respectively. These particular PAs, sugars, and amino acids differentially or commonly regulated by GABA could play critical roles in osmotic adjustment, osmoprotection, antioxidant, energy source, and signal molecular for creeping bentgrass to acclimate diverse abiotic stresses.

Keywords:  Amino acid; Drought; Heat; Metabolism; Osmotic adjustment; Salt; Sugar

DOI:  https://doi.org/10.1016/j.plaphy.2020.10.025
PLoS Genet. 2020 Oct;16(10): e1009085

DNA supercoiling differences in bacteria result from disparate DNA gyrase activation by polyamines.

Alexandre Duprey, Eduardo A Groisman.

DNA supercoiling is essential for all living cells because it controls all processes involving DNA. In bacteria, global DNA supercoiling results from the opposing activities of topoisomerase I, which relaxes DNA, and DNA gyrase, which compacts DNA. These enzymes are widely conserved, sharing >91% amino acid identity between the closely related species Escherichia coli and Salmonella enterica serovar Typhimurium. Why, then, do E. coli and Salmonella exhibit different DNA supercoiling when experiencing the same conditions? We now report that this surprising difference reflects disparate activation of their DNA gyrases by the polyamine spermidine and its precursor putrescine. In vitro, Salmonella DNA gyrase activity was sensitive to changes in putrescine concentration within the physiological range, whereas activity of the E. coli enzyme was not. In vivo, putrescine activated the Salmonella DNA gyrase and spermidine the E. coli enzyme. High extracellular Mg2+ decreased DNA supercoiling exclusively in Salmonella by reducing the putrescine concentration. Our results establish the basis for the differences in global DNA supercoiling between E. coli and Salmonella, define a signal transduction pathway regulating DNA supercoiling, and identify potential targets for antibacterial agents.

DOI: https://doi.org/10.1371/journal.pgen.1009085
Bot Stud. 2020 Oct 30. 61(1): 28

Physiological and transcriptome changes induced by exogenous putrescine in anthurium under chilling stress.

Xiangli Sun, Zebin Yuan, Bo Wang, Liping Zheng, Jianzhong Tan, Fadi Chen.

   BACKGROUND: Chilling stress is the major factor limiting plant productivity and quality in most regions of the world. In the present study, we aimed to evaluate the effects of putrescine (Put) and polyamine inhibitor D-arginine (D-arg) on the chilling tolerance of anthurium (Anthurium andraeanum).
RESULTS: Anthurium seedlings were pretreated with five different concentrations of Put solution or D-arg solution. Subsequently, the seedlings were subjected to chilling stress at 6 °C for 3 days, followed by a recovery at 25 °C for 1 day. Relative permeability of the plasma membrane, as well as physiological and morphologic parameters was assessed during the experiments. Additionally, transcriptome sequencing and patterns of differential gene expression related to chilling response were analyzed by qRT-PCR in 1.0 mM Put-treated and untreated anthurium seedlings. Results indicated that the supplementation of exogenous Put decreased the extent of membrane lipid peroxidation and the accumulation of malondialdehyde (MDA), promoted the antioxidant activities and proline content and maintained the morphologic performances compared with the control group. This finding indicated that the application of exogenous Put could effectively decrease the injury and maintain the quality of anthurium under chilling conditions. In contrast, the treatment of D-arg exhibited the opposite effects, which confirmed the effects of Put.
CONCLUSIONS: This research provided a possible approach to enhance the chilling tolerance of anthurium and reduce the energy consumption used in anthurium production.

Keywords:  Anthurium; Chilling stress; Physiological indices; Putrescine; Transcriptome analysis

DOI:  https://doi.org/10.1186/s40529-020-00305-2
Histochem Cell Biol. 2020 Oct 27.

Voluntary activity reverses spermidine-induced myocardial fibrosis and lipid accumulation in the obese male mouse.

Christian Mühlfeld, Clara Pfeiffer, Vanessa Schneider, Melanie Bornemann, Julia Schipke.

  Obesity due to high calorie intake induces cardiac hypertrophy and dysfunction, thus contributing to cardiovascular morbidity and mortality. Recent studies in aging suggest that oral supplementation with the natural polyamine spermidine has a cardioprotective effect. Here, the hypothesis was tested that spermidine or voluntary activity alone or in combination protect the heart from adverse effects induced by obesity. Therefore, C57Bl/6 mice (n = 8-10 per group) were subjected to control or high fat diet (HFD) and were left untreated, or either received spermidine via drinking water or were voluntarily active or both. After 30 weeks, the mice were killed and the left ventricle of the hearts was processed for light and electron microscopy. Design-based stereology was used to estimate parameters of hypertrophy, fibrosis, and lipid accumulation. HFD induced cardiac hypertrophy as demonstrated by higher volumes of the left ventricle, cardiomyocytes, interstitium, myofibrils and cardiomyocyte mitochondria. These changes were not influenced by spermidine or voluntary activity. HFD also induced myocardial fibrosis and accumulation of lipid droplets within cardiomyocytes. These HFD effects were enhanced in spermidine treated animals but not in voluntarily active mice. This was even the case in voluntarily active mice that received spermidine. In conclusion, the data confirm the induction of left ventricular hypertrophy by high-fat diet and suggest that-under high fat diet-spermidine enhances cardiomyocyte lipid accumulation and interstitial fibrosis which is counteracted by voluntary activity.

Keywords:  Heart; Hypertrophy; Myocardium; Obesity; Spermidine; Stereology; Voluntary activity

DOI:  https://doi.org/10.1007/s00418-020-01926-1