bims-polyam 2021-03-14 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–03–14
eight papers selected by
Sebastian J. Hofer, University of Graz

Spermidine supplementation in rare translation-associated disorders.
Roles of nitric oxide and polyamines in brain tumor growth.
Cadmium-resistant and arginine decarboxylase-producing endophytic Sphingomonas sp. C40 decreases cadmium accumulation in host rice (Oryza sativa Cliangyou 513).
Effect of spermidine on biofilm formation in Escherichia coli K-12.
Chemoprotective effect of atorvastatin against benzo(a)pyrene-induced lung cancer via the inhibition of oxidative stress and inflammatory parameters.
Accuracy and uniformity of the nomenclature of biogenic amines and polyamines in metabolomics studies: A preliminary study.
Impact of Phosphate Availability on Membrane Lipid Content of the Model Strains, Streptomyces lividans and Streptomyces coelicolor.
Bacterial infection reinforces host metabolic flux from arginine to spermine for NLRP3 inflammasome evasion.

Cell Stress. 2021 Mar 08. 5(3): 29-32

Spermidine supplementation in rare translation-associated disorders.

Andreas Zimmermann, Didac Carmona-Gutierrez, Frank Madeo.

  The polyamine spermidine is essential for protein translation in eukaryotes, both as a substrate for the hypusination of the translation initiation factor eIF5A as well as general translational fidelity. Dwindling spermidine levels during aging have been implicated in reduced immune cell function through insufficient eIF5A hypusination, which can be restored by external supplementation. Recent findings characterize a group of novel Mendelian disorders linked to EIF5A missense and nonsense variants that cause protein translation defects. In model organisms that recapitulate these mutations, spermidine supplementation was able to alleviate at least some of the concomitant protein translation defects. Here, we discuss the role of spermidine in protein translation and possible therapeutic avenues for translation-associated disorders.

Keywords:  Kabuki syndrome; eIF5A; hypusination; rare disease; spermidine; translation

DOI:  https://doi.org/10.15698/cst2021.03.243
Adv Med Sci. 2021 Mar 09. pii: S1896-1126(21)00014-6. [Epub ahead of print]66(1): 199-205

Roles of nitric oxide and polyamines in brain tumor growth.

Monika Szeliga, Jan Albrecht.

  Nitric oxide (NO) and polyamines: putrescine, spermidine and spermine, are key arginine metabolites in mammalian tissues that play critical roles i.a. in regulation of vascular tone (NO), and cell cycle regulation (polyamines). In the brain, both classes of molecules additionally have neuromodulatory and neuroprotective potential, and NO also a neurotoxic potential. Here we review evidence that brain tumors use the NO- and polyamine-synthesizing machineries to the benefit of their differentiation and growth from healthy glia and neurons. With a few exceptions, brain tumors show increased activities of one or all of the three arginine (Arg) to NO-converting nitric oxide synthase (NOS) isoforms (iNOS, eNOS, nNOS), but also elevated activities of polyamines-generating and modifying enzymes: arginase I/II, ornithine decarboxylase and spermidine/spermine N1-acetyltransferase. The degree of stimulation of NO- and polyamine synthesis often correlates with brain tumor malignancy. Excess NO, but also spermine, spermidine and their N1-acetylated forms, are tumor- and context-dependently involved in angiogenesis, tumor initiation and growth, and resistance to chemo- or radiotherapy. Hypothetically, increased demand for NO and/or polyamines is likely to contribute to Arg auxotrophy of malignant brain tumors, albeit the causal nexus awaits experimental verification.

Keywords:  Arginine; Brain tumor; Malignancy; Nitric oxide; Polyamines

DOI:  https://doi.org/10.1016/j.advms.2021.02.006
Chemosphere. 2021 Mar 01. pii: S0045-6535(21)00578-6. [Epub ahead of print]275 130109

Cadmium-resistant and arginine decarboxylase-producing endophytic Sphingomonas sp. C40 decreases cadmium accumulation in host rice (Oryza sativa Cliangyou 513).

Cheng Cheng, Ru Wang, Lijing Sun, Linyan He, Xiafang Sheng.

  In this study, an cadmium (Cd)-immobilizing and arginine decarboxylase-producing endophytic Sphingomonas sp. strain C40 obtained from the seeds of Oryza sativa Cliangyou 513 was characterized for its Cd availability and Cd uptake in host rice using hydroponic and soil experiments. The Cd concentration decreased by 51-95% compared to the control, while the spermidine concentration increased by 19-25% with Cd compared with no Cd in the strain C40-inoculated solution. Strain C40 decreased the above-ground tissue Cd content by 27-37% and increased spermine and spermidine contents by 28-67% and the expression levels of genes involved in spermine and spermidine production by 29-217% in rice roots compared to the controls. Furthermore, correlation analyses showed the significantly negative correlation between rice root spermine and spermidine contents and above-ground tissue Cd content. In the Cd-added soil, strain C40 promoted the rice biomass by 29-36% and decreased rice root, above-ground tissue, and grain Cd contents by 18, 16, and 33% and total grain Cd uptake by 14% compared with the controls at the maturity stage. Strain C40 decreased the exchangeable Cd content by 27% and increased the Fe and Mn oxides-bound Cd content by 45% in the rice rhizosphere soils at the maturity stage compared with the controls. These results suggested that the endophytic bacterial strain C40 increased rice root polyamine production and their related gene expression and the transformation of available Cd to unavailable Cd, leading to reduced Cd accumulation and translocation from the rice roots to grains.

Keywords:  Cd immobilization; Cd uptake in rice; Gene expression of polyamine production; Polyamine; Rice endophytic bacteria

DOI:  https://doi.org/10.1016/j.chemosphere.2021.130109
J Bacteriol. 2021 Mar 08. pii: JB.00652-20. [Epub ahead of print]

Effect of spermidine on biofilm formation in Escherichia coli K-12.

Kullathida Thongbhubate, Yuko Nakafuji, Rina Matsuoka, Sanomi Kakegawa, Hideyuki Suzuki.

Polyamines are essential for biofilm formation in Escherichia coli, but it is still unclear which polyamines are primarily responsible for this phenomenon. To address this issue, we constructed a series of E. coli K-12 strains with mutations in genes required for the synthesis and metabolism of polyamines. Disruption of the spermidine synthase gene (speE) caused a severe defect in biofilm formation. This defect was rescued by the addition of spermidine to the medium, but not by putrescine or cadaverine. A multidrug/spermidine efflux pump membrane subunit (MdtJ)-deficient strain was anticipated to accumulate more spermidine and result in enhanced biofilm formation than the MdtJ+ strain. However, the mdtJ mutation did not affect intracellular spermidine or biofilm concentrations. E. coli has the spermidine acetyltransferase (SpeG) and glutathionylspermidine synthetase/amidase (Gss) to metabolize intracellular spermidine. Under the biofilm-forming condition, not Gss but SpeG plays a major role in decreasing the too high intracellular spermidine concentrations. Additionally, PotFGHI can function as a compensatory importer of spermidine when PotABCD is absent under the biofilm-forming condition. Lastly, we reported here that, in addition to intracellular spermidine, the periplasmic binding protein (PotD) of the spermidine preferential ABC transporter is essential for stimulating biofilm formation.IMPORTANCEPrevious reports have speculated on the effect of polyamines on bacterial biofilm formation. However, the regulation of biofilm formation by polyamines in Escherichia coli has not yet been assessed. The identification of polyamines that stimulate biofilm formation is important for developing novel therapies for biofilm-forming pathogens. This study sheds light on biofilm regulation in E. coli Our findings provide conclusive evidence that only spermidine can stimulate biofilm formation in E. coli cells, but not putrescine and cadaverine. Lastly, ΔpotD inhibits biofilm formation even though the spermidine is synthesized inside the cells from putrescine. Since PotD is significant for biofilm formation and there is no ortholog of PotABCD transporter in humans, PotD could be a target for the development of biofilm inhibitors.

DOI: https://doi.org/10.1128/JB.00652-20
Ann Transl Med. 2021 Feb;9(4): 355

Chemoprotective effect of atorvastatin against benzo(a)pyrene-induced lung cancer via the inhibition of oxidative stress and inflammatory parameters.

Xusheng Du, Dongfan Li, Guanjie Wang, Yali Fan, Namiao Li, Lili Chai, Guangshun Li, Jianying Li.

   Background: Lung cancer affects approximately 9% of women and 17% of men worldwide, and has a mortality rate of 17%. Previously published studies have suggested that oxidative stress expansion can lead to lung cancer. The aim of the current study was to analyze the possible inhibitory pathway of atorvastatin against lung cancer cells in an in vivo model.
Methods: The cytotoxic effects of atorvastatin on lung cancer cell lines H460 and A549 were analyzed, as well as cell cycle arrest and cell morphology. Benzo(a)pyrene (BaP) was used for the induction of lung cancer in experimental rats, and atorvastatin (5, 10, and 20 mg/kg body weight) was used for treatment in a dose-dependent manner. Body weight and lung tumors were calculated at regular intervals. Antioxidants, pro-inflammatory cytokines, phase I and II antioxidant enzymes, polyamine enzymes, and apoptosis markers were determined at end of the experimental study.
Results: Cell cycle arrest occurred at the G2/M phase after atorvastatin treatment. Atorvastatin increased cytochrome C expression and caspase activity in a dose-dependent manner, and increased the activity of antioxidative enzymes, such as GPx, SOD, GST, reduced glutathione, and catalase, and reduced the level of nitrate and LPO. It also altered the xanthine oxidase (XO), Lactic Acid Dehydrogenase (LDH), quinone reductase (QR), UDP-glucuronosyltransferase (UDP-GT), adenosine deaminase (ADA), Aryl hydrocarbon hydroxylase (AHH), 5'-nucleotidase, cytochrome P450, cytochrome B5 and NADPH cytochrome C reductase levels. Atorvastatin was found to modulate polyamine enzyme levels, such as histamine, spermine, spermidine, and putrescine, and significantly (P<0.001) reduced the pro-inflammatory cytokine levels, such as tumor necrosis factor-α. Interleukin (IL)-6 and interleukin-1β (IL-1β) increased caspase-3 and caspase-9 levels in a dose-dependent manner.
Conclusions: Our findings indicate that atorvastatin can inhibit lung cancer through apoptosis.

Keywords:  Atorvastatin; apoptosis; caspase; inflammation; lung cancer

DOI:  https://doi.org/10.21037/atm-20-7770
Biochem Mol Biol Educ. 2021 Mar 08.

Accuracy and uniformity of the nomenclature of biogenic amines and polyamines in metabolomics studies: A preliminary study.

Omer Akyol, Kylie Tessier, Sumeyya Akyol.

  Metabolomics is one of the newest areas in biochemistry dedicated to investigating small biomolecules in biofluids, tissues, and cells. Cutting edge instruments used in metabolomics studies make it possible to identify thousands of biomolecules and determine their interactions with biological networks. This tremendous area has increased the significance of accurate chemical nomenclature of compounds. Therefore, the classification of the organic molecules has become one of the most important issues in the field. Biogenic amines are nitrogenous compounds of low molecular weight formed by the decarboxylation of amino acids or by the amination and the transamination of aldehydes and ketones during normal metabolic processes. This letter covers the topic of nomenclature with respect to the current usage of biogenic amines in scientific literature. We use metabolomics as an example of field reporting data on trace levels of molecules that may be miscategorized in primary literature. We suggest that the incorrect classification of molecules will influence science education adversely because resources used for teaching are drawn from primary literature references that may contain errors.

Keywords:  biogenic amines; misclassification; nomenclature

DOI:  https://doi.org/10.1002/bmb.21497
Front Microbiol. 2021 ;12 623919

Impact of Phosphate Availability on Membrane Lipid Content of the Model Strains, Streptomyces lividans and Streptomyces coelicolor.

Clara Lejeune, Sonia Abreu, Pierre Chaminade, Thierry Dulermo, Michelle David, Sebastiaan Werten, Marie-Joelle Virolle.

  In this issue we demonstrated that the phospholipid content of Streptomyces lividans varies greatly with Pi availability being was much lower in Pi limitation than in Pi proficiency whereas that of Streptomyces coelicolor varied little with Pi availability. In contrast the content in phosphate free ornithine lipids was enhanced in both strains in condition of phosphate limitation. Ornithine lipids biosynthesis starts with the N-acylation of ornithine to form lyso-ornithine that is then O-acylated to yield ornithine lipid. The operon sco1222-23 was proposed to be involved in the conversion of specific amino acids into ornithine in condition of phosphate limitation whereas the sco0921-20 operon encoding N- and O-acyltransferase, respectively, was shown to be involved in the biosynthesis of these lipids. The expression of these two operons was shown to be under the positive control of the two components system PhoR/PhoP and thus induced in phosphate limitation. The expression of phoR/phoP being weak in S. coelicolor, the poor expression of these operons resulted into a fivefold lower ornithine lipids content in this strain compared to S. lividans. In the deletion mutant of the sco0921-20 operon of S. lividans, lyso-ornithine and ornithine lipids were barely detectable and TAG content was enhanced. The complementation of this mutant by the sco0921-20 operon or by sco0920 alone restored ornithine lipids and TAG content to wild type level and was correlated with a twofold increase in the cardiolipin content. This suggested that SCO0920 bears, besides its broad O-acyltransferase activity, an N-acyltransferase activity and this was confirmed by the detection of lyso-ornithine in this strain. In contrast, the complementation of the mutant by sco0921 alone had no impact on ornithine lipids, TAG nor cardiolipin content but was correlated with a high lyso-ornithine content. This confirmed that SCO0921 is a strict N-acyltransferase. However, interestingly, the over-expression of the sco0921-20 operon or of sco0921 alone in S. coelicolor, led to an almost total disappearance of phosphatidylinositol that was correlated with an enhanced DAG and TAG content. This suggested that SCO0921 also acts as a phospholipase C, degrading phosphatidylinositol to indirectly supply of phosphate in condition of phosphate limitation.

Keywords:  acyltransferase; hemolysin; ornithine lipids; phosphate limitation; phosphatidylinositol; phospholipase C; phospholipids; triacylglycerol

DOI:  https://doi.org/10.3389/fmicb.2021.623919
Cell Rep. 2021 Mar 09. pii: S2211-1247(21)00146-7. [Epub ahead of print]34(10): 108832

Bacterial infection reinforces host metabolic flux from arginine to spermine for NLRP3 inflammasome evasion.

Jiatiao Jiang, Wenwen Wang, Fei Sun, Yuanxing Zhang, Qin Liu, Dahai Yang.

  Hosts recognize cytosolic microbial infection via the nucleotide-binding domain-like receptor (NLR) protein family, triggering inflammasome complex assembly to provoke pyroptosis or cytokine-related caspase-1-dependent antimicrobial responses. Pathogens have evolved diverse strategies to antagonize inflammasome activation. Here, Edwardsiella piscicida gene-defined transposon library screening for lactate dehydrogenase (LDH) release in nlrc4-/- bone marrow-derived macrophages (BMDMs) demonstrates that genes clustered in the bacterial arginine metabolism pathway participate in NLRP3 inflammasome inhibition. Blocking arginine uptake or putrescine export significantly relieves NLRP3 inflammasome inhibition, indicating that this bacterium rewires its arginine metabolism network during infection. Moreover, intracellular E. piscicida recruits the host arginine importer (mCAT-1) and putrescine exporter (Oct-2) to bacterium-containing vacuoles, accompanied by reduced arginine and accumulated cytosolic spermine. Neutralizing E. piscicida-induced cytosolic spermine enhancement by spermine synthetase or extracellular spermine significantly alters NLRP3 inflammasome activation. Importantly, accumulated cytosolic spermine inhibits K+ efflux-dependent NLRP3 inflammasome activation. These data highlight the mechanism of bacterial gene-mediated arginine metabolism control for NLRP3 inflammasome evasion.

Keywords:  Edwardsiella piscicida; K(+) efflux; NLRP3 inflammasome; arginine metabolism; spermine

DOI:  https://doi.org/10.1016/j.celrep.2021.108832