bims-polyam 2022-11-27 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2022–11–27
eight papers selected by
Sebastian J. Hofer, University of Graz

Foliar Application of Spermidine Alleviates Waterlogging-Induced Damages to Maize Seedlings by Enhancing Antioxidative Capacity, Modulating Polyamines and Ethylene Biosynthesis.
Effect of Pd2Spermine on Mice Brain-Liver Axis Metabolism Assessed by NMR Metabolomics.
The Multidrug Efflux Regulator AcrR of Escherichia coli Responds to Exogenous and Endogenous Ligands To Regulate Efflux and Detoxification.
Simultaneous Action of Silymarin and Dopamine Enhances Defense Mechanisms Related to Antioxidants, Polyamine Metabolic Enzymes, and Tolerance to Cadmium Stress in Phaseolus vulgaris.
Omics Markers of Red Blood Cell Transfusion in Trauma.
Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis.
Polyamines Promote Aragonite Nucleation and Generate Biomimetic Structures.
A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes.

Life (Basel). 2022 Nov 18. pii: 1921. [Epub ahead of print]12(11):

Foliar Application of Spermidine Alleviates Waterlogging-Induced Damages to Maize Seedlings by Enhancing Antioxidative Capacity, Modulating Polyamines and Ethylene Biosynthesis.

Xiuling Wang, Qun Wang, Moubiao Zhang, Yulong Zhao, Pengfei Dong, Yali Zhao, Hongping Li, Xucun Jia, Panpan An, Yulou Tang, Chaohai Li.

  Waterlogging is a major threat to maize production worldwide. The exogenous application of spermidine is well known to enhance plant tolerance to abiotic stresses. The role of exogenous spermidine application in waterlogging tolerance in maize was investigated in this study. Two maize varieties (a waterlogging-tolerant variety: Xundan 20 (XD20) and a waterlogging-sensitive variety: Denghai 662 (DH662)) were subjected to waterlogging stress at the seedling stage, and then foliar spraying of 0.75 mM spermidine or purified water. Findings demonstrated lower chlorophyll content, reduced growth indices, considerable increase in superoxide anion (O2-) generation rate, and H2O2/malondialdehyde accumulation in the two maize varieties under waterlogging stress compared to the control treatment. However, the tolerance variety performed better than the sensitive one. Foliar application of spermidine significantly increased antioxidant enzyme activities under waterlogging stress. In addition, the application of spermidine increased polyamine levels and led to the reduction of ethylene levels under waterlogging. Consequences of spermidine application were most apparent for the waterlogging-sensitive cultivar DH662 under waterlogging than the waterlogging-tolerant variety XD20.

Keywords:  abiotic stress; antioxidant defense; ethylene biosynthesis; polyamine; spermidine

DOI:  https://doi.org/10.3390/life12111921
Int J Mol Sci. 2022 Nov 09. pii: 13773. [Epub ahead of print]23(22):

Effect of Pd2Spermine on Mice Brain-Liver Axis Metabolism Assessed by NMR Metabolomics.

Tatiana J Carneiro, Martin Vojtek, Salomé Gonçalves-Monteiro, Ana L M Batista de Carvalho, Maria Paula M Marques, Carmen Diniz, Ana M Gil.

  Cisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound Pd2Spermine (Pd2Spm) has emerged as a potential alternative drug, with favorable pharmacokinetic/pharmacodynamic properties. This paper reports on a Nuclear Magnetic Resonance metabolomics study to (i) characterize the response of mice brain and liver to Pd2Spm, compared to cDDP, and (ii) correlate brain-liver metabolic variations. Multivariate and correlation analysis of the spectra of polar and lipophilic brain and liver extracts from an MDA-MB-231 cell-derived mouse model revealed a stronger impact of Pd2Spm on brain metabolome, compared to cDDP. This was expressed by changes in amino acids, inosine, cholate, pantothenate, fatty acids, phospholipids, among other compounds. Liver was less affected than brain, with cDDP inducing more metabolite changes. Results suggest that neither drug induces neuronal damage or inflammation, and that Pd2Spm seems to lead to enhanced brain anti-inflammatory and antioxidant mechanisms, regulation of brain bioactive metabolite pools and adaptability of cell membrane characteristics. The cDDP appears to induce higher extension of liver damage and an enhanced need for liver regeneration processes. This work demonstrates the usefulness of untargeted metabolomics in evaluating drug impact on multiple organs, while confirming Pd2Spm as a promising replacement of cDDP.

Keywords:  NMR; Pd2Spm; brain; cisplatin; liver; metabolomics; mice; palladium(II); platinum(II); spermine

DOI:  https://doi.org/10.3390/ijms232213773
mSphere. 2022 Nov 23. e0047422

The Multidrug Efflux Regulator AcrR of Escherichia coli Responds to Exogenous and Endogenous Ligands To Regulate Efflux and Detoxification.

Dana E Harmon, Cristian Ruiz.

  The transcriptional repressor AcrR is the main regulator of the multidrug efflux pump AcrAB-TolC, which plays a major role in antibiotic resistance and cell physiology in Escherichia coli and other Enterobacteriaceae. However, it remains unknown which ligands control the function of AcrR. To address this gap in knowledge, this study tested whether exogenous and/or endogenous molecules identified as potential AcrR ligands regulate the activity of AcrR. Using electrophoretic mobility shift assays (EMSAs) with purified AcrR and the acrAB promoter and in vivo gene expression experiments, we found that AcrR responds to both exogenous molecules and cellular metabolites produced by E. coli. In total, we identified four functional ligands of AcrR, ethidium bromide (EtBr), an exogenous antimicrobial known to be effluxed by the AcrAB-TolC pump and previously shown to bind to AcrR, and three polyamines produced by E. coli, namely, putrescine, cadaverine, and spermidine. We found that EtBr and polyamines bind to AcrR both in vitro and in vivo, which prevents the binding of AcrR to the acrAB promoter and, ultimately, induces the expression of acrAB. Finally, we also found that AcrR contributes to mitigating the toxicity produced by excess polyamines by directly regulating the expression of AcrAB-TolC and two previously unknown AcrR targets, the MdtJI spermidine efflux pump and the putrescine degradation enzyme PuuA. Overall, these findings significantly expand our understanding of the function of AcrR by revealing that this regulator responds to different exogenous and endogenous ligands to regulate the expression of multiple genes involved in efflux and detoxification. IMPORTANCE Multidrug efflux pumps can remove antibiotics and other toxic molecules from cells and are major contributors to antibiotic resistance and bacterial physiology. Therefore, it is essential to better understand their function and regulation. AcrAB-TolC is the main multidrug efflux pump in the Enterobacteriaceae family, and AcrR is its major transcriptional regulator. However, little is known about which ligands control the function of AcrR or which other genes are controlled by this regulator. This study contributes to addressing these gaps in knowledge by showing that (i) the activity of AcrR is controlled by the antimicrobial ethidium bromide and by polyamines produced by E. coli, and (ii) AcrR directly regulates the expression of AcrAB-TolC and genes involved in detoxification and efflux of excess polyamines. These findings significantly advance our understanding of the biological role of AcrR by identifying four ligands that control its function and two novel targets of this regulator.

Keywords:  AcrAB-TolC; AcrR; Escherichia coli; ethidium bromide; ligand; multidrug efflux pump; polyamines

DOI:  https://doi.org/10.1128/msphere.00474-22
Plants (Basel). 2022 Nov 12. pii: 3069. [Epub ahead of print]11(22):

Simultaneous Action of Silymarin and Dopamine Enhances Defense Mechanisms Related to Antioxidants, Polyamine Metabolic Enzymes, and Tolerance to Cadmium Stress in Phaseolus vulgaris.

Awatif M Abdulmajeed, Basmah M Alharbi, Hesham F Alharby, Amani M Abualresh, Ghada A Badawy, Wael M Semida, Mostafa M Rady.

  Silymarin (Sm) and dopamine (DA) act synergistically as potential antioxidants, mediating many physiological and biochemical processes. As a first report, we investigated the synergistic effect of Sm and DA in mitigating cadmium stress in Phaseolus vulgaris plants. Three experiments were conducted simultaneously using 40 cm diameter pots to elucidate how Sm and DA affect cadmium tolerance traits at morphological, physiological, and biochemical levels. Cadmium stress triggered a marked reduction in growth, productivity, and physio-biochemical characteristics of common bean plants compared to unstressed plants. Seed priming (SP) and foliar spraying (FS) with silymarin (Sm) or dopamine (DA) ((DA (SP) + Sm (FS) and Sm (SP) + DA (FS)) ameliorated the damaging effects of cadmium stress. Sm seed priming + DA foliar spraying (Sm (SP) + DA (FS)) was more efficient. The treated stressed common bean plants showed greater tolerance to cadmium stress by diminishing oxidative stress biomarkers (i.e., O2•-, H2O2, and MDA) levels through enhanced enzymatic (SOD, CAT, POD, APX) and non-enzymatic (ascorbic acid, glutathione, α-tocopherol, choline, phenolics, flavonoids) antioxidant activities and osmoprotectants (proline, glycine betaine, and soluble sugars) contents, as well as through improved photosynthetic efficiency (total chlorophyll and carotenoids contents, photochemical activity, and efficiencies of carboxylation (iCE) and PSII (Fv/Fm)), polyamines (Put, Spd, and Spm), and polyamine metabolic enzymes (ADC and ODC) accumulation. These findings signify that Sm and DA have remarkable anti-stress effects, which can help regulate plant self-defense systems, reflecting satisfactory plant growth and productivity. Thus, realizing the synergistic effect of Sm and DA in cadmium tolerance confers potential new capabilities for these compounds to function in sustainable agriculture.

Keywords:  abiotic stress tolerance; anti-oxidative defense systems; cadmium stress; common bean; dopamine; silymarin

DOI:  https://doi.org/10.3390/plants11223069
Int J Mol Sci. 2022 Nov 10. pii: 13815. [Epub ahead of print]23(22):

Omics Markers of Red Blood Cell Transfusion in Trauma.

Ian S LaCroix, Mitchell Cohen, Ernest E Moore, Monika Dzieciatkowska, Travis Nemkov, Terry R Schaid, Margaret Debot, Kenneth Jones, Christopher C Silliman, Kirk C Hansen, Angelo D'Alessandro.

  Red blood cell (RBC) transfusion is a life-saving intervention for millions of trauma patients every year worldwide. While hemoglobin thresholds are clinically driving the need for RBC transfusion, limited information is available with respect to transfusion efficacy at the molecular level in clinically relevant cohorts. Here, we combined plasma metabolomic and proteomic measurements in longitudinal samples (n = 118; up to 13 time points; total samples: 690) from trauma patients enrolled in the control of major bleeding after trauma (COMBAT) study. Samples were collected in the emergency department and at continuous intervals up to 168 h (seven days) post-hospitalization. Statistical analyses were performed to determine omics correlate to transfusions of one, two, three, five, or more packed RBC units. While confounded by the concomitant transfusion of other blood components and other iatrogenic interventions (e.g., surgery), here we report that transfusion of one or more packed RBCs-mostly occurring within the first 4 h from hospitalization in this cohort-results in the increase in circulating levels of additive solution components (e.g., mannitol, phosphate) and decreases in the levels of circulating markers of hypoxia, such as lactate, carboxylic acids (e.g., succinate), sphingosine 1-phosphate, polyamines (especially spermidine), and hypoxanthine metabolites with potential roles in thromboinflammatory modulation after trauma. These correlations were the strongest in patients with the highest new injury severity scores (NISS > 25) and lowest base excess (BE < -10), and the effect observed was proportional to the number of units transfused. We thus show that transfusion of packed RBCs transiently increases the circulating levels of plasticizers-likely leaching from the blood units during refrigerated storage in the blood bank. Changes in the levels of arginine metabolites (especially citrulline to ornithine ratios) are indicative of an effect of transfusion on nitric oxide metabolism, which could potentially contribute to endothelial regulation. RBC transfusion was associated with changes in the circulating levels of coagulation factors, fibrinogen chains, and RBC-proteins. Changes in lysophospholipids and acyl-carnitines were observed upon transfusion, suggestive of an effect on the circulating lipidome-though cell-extrinsic/intrinsic effects and/or the contribution of other blood components cannot be disentangled. By showing a significant decrease in circulating markers of hypoxia, this study provides the first multi-omics characterization of RBC transfusion efficacy in a clinically relevant cohort of trauma patients.

Keywords:  erythrocyte; hemorrhagic shock; hypoxia; plasticizer; succinate; trauma

DOI:  https://doi.org/10.3390/ijms232213815
Int J Mol Sci. 2022 Nov 08. pii: 13738. [Epub ahead of print]23(22):

Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis.

Guorong Cheng, Zhiqiang Liu, Zhong Zheng, Fengrui Song, Xiaoyu Zhuang, Shu Liu.

  Metastasis is one of the main obstacles for the treatment and prognosis of breast cancer. In this study, the effects and possible mechanisms of aloe emodin (AE) and emodin (EMD) for inhibiting breast cancer metastasis were investigated via cell metabolomics. First, a co-culture model of MCF-7 and HUVEC cells was established and compared with a traditional single culture of MCF-7 cells. The results showed that HUVEC cells could promote the development of cancer cells to a malignant phenotype. Moreover, AE and EMD could inhibit adhesion, invasion, and angiogenesis and induce anoikis of MCF-7 cells in co-culture model. Then, the potential mechanisms behind AE and EMD inhibition of MCF-7 cell metastasis were explored using a metabolomics method based on UPLC-Q-TOF/MS multivariate statistical analysis. Consequently, 27 and 13 biomarkers were identified in AE and EMD groups, respectively, including polyamine metabolism, methionine cycle, TCA cycle, glutathione metabolism, purine metabolism, and aspartate synthesis. The typical metabolites were quantitatively analyzed, and the results showed that the inhibitory effect of AE was significantly better than EMD. All results confirmed that AE and EMD could inhibit metastasis of breast cancer cells through different pathways. Our study provides an overall view of the underlying mechanisms of AE and EMD against breast cancer metastasis.

Keywords:  aloe emodin (AE); breast cancer; cell metabolomics; emodin (EMD); metastasis

DOI:  https://doi.org/10.3390/ijms232213738
Adv Sci (Weinh). 2022 Nov 20. e2203759

Polyamines Promote Aragonite Nucleation and Generate Biomimetic Structures.

Ouassef Nahi, Alexander N Kulak, Shuheng Zhang, Xuefeng He, Zabeada Aslam, Martha A Ilett, Ian J Ford, Robert Darkins, Fiona C Meldrum.

  Calcium carbonate biomineralization is remarkable for the ability of organisms to produce calcite or aragonite with perfect fidelity, where this is commonly attributed to specific anionic biomacromolecules. However, it is proven difficult to mimic this behavior using synthetic or biogenic anionic organic molecules. Here, it is shown that cationic polyamines ranging from small molecules to large polyelectrolytes can exert exceptional control over calcium carbonate polymorph, promoting aragonite nucleation at extremely low concentrations but suppressing its growth at high concentrations, such that calcite or vaterite form. The aragonite crystals form via particle assembly, giving nanoparticulate structures analogous to biogenic aragonite, and subsequent growth yields stacked aragonite platelets comparable to structures seen in developing nacre. This mechanism of polymorph selectivity is captured in a theoretical model based on these competing nucleation and growth effects and is completely distinct from the activity of magnesium ions, which generate aragonite by inhibiting calcite. Profiting from these contrasting mechanisms, it is then demonstrated that polyamines and magnesium ions can be combined to give unprecedented control over aragonite formation. These results give insight into calcite/aragonite polymorphism and raise the possibility that organisms may exploit both amine-rich organic molecules and magnesium ions in controlling calcium carbonate polymorph.

Keywords:  biomineralization; calcium carbonate; magnesium; non-classical crystallization; polymorph

DOI:  https://doi.org/10.1002/advs.202203759
Diagnostics (Basel). 2022 Nov 21. pii: 2881. [Epub ahead of print]12(11):

A Study of the Metabolic Pathways Affected by Gestational Diabetes Mellitus: Comparison with Type 2 Diabetes.

Loukia Spanou, Aikaterini Dimou, Christina E Kostara, Eleni Bairaktari, Eleni Anastasiou, Vasilis Tsimihodimos.

   BACKGROUND: Gestational diabetes mellitus (GDM) remains incompletely understood and increases the risk of developing Diabetes mellitus type 2 (DM2). Metabolomics provides insights etiology and pathogenesis of disease and discovery biomarkers for accurate detection. Nuclear magnetic resonance (NMR) spectroscopy is a key platform defining metabolic signatures in intact serum/plasma. In the present study, we used NMR-based analysis of macromolecules free-serum to accurately characterize the altered metabolic pathways of GDM and assessing their similarities to DM2. Our findings could contribute to the understanding of the pathophysiology of GDM and help in the identification of metabolomic markers of the disease.
METHODS: Sixty-two women with GDM matched with seventy-seven women without GDM (control group). 1H NMR serum spectra were acquired on an 11.7 T Bruker Avance DRX NMR spectrometer.
RESULTS: We identified 55 metabolites in both groups, 25 of which were significantly altered in the GDM group. GDM group showed elevated levels of ketone bodies, 2-hydroxybutyrate and of some metabolic intermediates of branched-chain amino acids (BCAAs) and significantly lower levels of metabolites of one-carbon metabolism, energy production, purine metabolism, certain amino acids, 3-methyl-2-oxovalerate, ornithine, 2-aminobutyrate, taurine and trimethylamine N-oxide.
CONCLUSION: Metabolic pathways affected in GDM were beta-oxidation, ketone bodies metabolism, one-carbon metabolism, arginine and ornithine metabolism likewise in DM2, whereas BCAAs catabolism and aromatic amino acids metabolism were affected, but otherwise than in DM2.

Keywords:  biomarkers; gestational diabetes mellitus (GDM); macromolecules free-serum; metabolomics; nuclear magnetic resonance (NMR) spectroscopy; pathway analysis; personalized medicine; pregnancy; type 2 diabetes

DOI:  https://doi.org/10.3390/diagnostics12112881