bims-polyam 2019-06-02 papers

on Polyamines

Issue of 2019–06–02
nine papers selected by
Sebastian J. Hofer, University of Graz and Alexander Ivanov, Engelhardt Institute of Molecular Biology

Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation.
Polyamine Catabolism in Plants: A Universal Process With Diverse Functions.
Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers.
Spermidine Synthase (SPDS) Undergoes Concerted Structural Rearrangements Upon Ligand Binding - A Case Study of the Two SPDS Isoforms From Arabidopsis thaliana.
Microbiome-metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease.
Single-Cell Transcriptome Analysis Reveals Estrogen Signaling Coordinately Augments One-Carbon, Polyamine, and Purine Synthesis in Breast Cancer.
Characterization of a highly conserved Antheraea pernyi spermidine synthase gene.
Arabidopsis ABCG28 is required for the apical accumulation of reactive oxygen species in growing pollen tubes.
Photorespiratory serine hydroxymethyltransferase 1 activity impacts abiotic stress tolerance and stomatal closure.

Cell Metab. 2019 May 17. pii: S1550-4131(19)30243-8. [Epub ahead of print]

Polyamines and eIF5A Hypusination Modulate Mitochondrial Respiration and Macrophage Activation.

Daniel J Puleston, Michael D Buck, Ramon I Klein Geltink, Ryan L Kyle, George Caputa, David O'Sullivan, Alanna M Cameron, Angela Castoldi, Yaarub Musa, Agnieszka M Kabat, Ying Zhang, Lea J Flachsmann, Cameron S Field, Annette E Patterson, Stefanie Scherer, Francesca Alfei, Francesc Baixauli, S Kyle Austin, Beth Kelly, Mai Matsushita, Jonathan D Curtis, Katarzyna M Grzes, Matteo Villa, Mauro Corrado, David E Sanin, Jing Qiu, Nora Pällman, Katelyn Paz, Maria Elena Maccari, Bruce R Blazar, Gerhard Mittler, Joerg M Buescher, Dietmar Zehn, Sabine Rospert, Edward J Pearce, Stefan Balabanov, Erika L Pearce.

  How cells adapt metabolism to meet demands is an active area of interest across biology. Among a broad range of functions, the polyamine spermidine is needed to hypusinate the translation factor eukaryotic initiation factor 5A (eIF5A). We show here that hypusinated eIF5A (eIF5AH) promotes the efficient expression of a subset of mitochondrial proteins involved in the TCA cycle and oxidative phosphorylation (OXPHOS). Several of these proteins have mitochondrial targeting sequences (MTSs) that in part confer an increased dependency on eIF5AH. In macrophages, metabolic switching between OXPHOS and glycolysis supports divergent functional fates stimulated by activation signals. In these cells, hypusination of eIF5A appears to be dynamically regulated after activation. Using in vivo and in vitro models, we show that acute inhibition of this pathway blunts OXPHOS-dependent alternative activation, while leaving aerobic glycolysis-dependent classical activation intact. These results might have implications for therapeutically controlling macrophage activation by targeting the polyamine-eIF5A-hypusine axis.

Keywords:  deoxyhypusine hydroxylase; deoxyhypusine synthase; eIF5A; hypusination; immunometabolism; macrophage activation; metabolism; polyamines

DOI:  https://doi.org/10.1016/j.cmet.2019.05.003
Front Plant Sci. 2019 ;10 561

Polyamine Catabolism in Plants: A Universal Process With Diverse Functions.

Wei Wang, Konstantinos Paschalidis, Jian-Can Feng, Jie Song, Ji-Hong Liu.

  Polyamine (PA) catabolic processes are performed by copper-containing amine oxidases (CuAOs) and flavin-containing PA oxidases (PAOs). So far, several CuAOs and PAOs have been identified in many plant species. These enzymes exhibit different subcellular localization, substrate specificity, and functional diversity. Since PAs are involved in numerous physiological processes, considerable efforts have been made to explore the functions of plant CuAOs and PAOs during the recent decades. The stress signal transduction pathways usually lead to increase of the intracellular PA levels, which are apoplastically secreted and oxidized by CuAOs and PAOs, with parallel production of hydrogen peroxide (H2O2). Depending on the levels of the generated H2O2, high or low, respectively, either programmed cell death (PCD) occurs or H2O2 is efficiently scavenged by enzymatic/nonenzymatic antioxidant factors that help plants coping with abiotic stress, recruiting different defense mechanisms, as compared to biotic stress. Amine and PA oxidases act further as PA back-converters in peroxisomes, also generating H2O2, possibly by activating Ca2+ permeable channels. Here, the new research data are discussed on the interconnection of PA catabolism with the derived H2O2, together with their signaling roles in developmental processes, such as fruit ripening, senescence, and biotic/abiotic stress reactions, in an effort to elucidate the mechanisms involved in crop adaptation/survival to adverse environmental conditions and to pathogenic infections.

Keywords:  ROS; abiotic and biotic stress; fruit ripening and senescence; plant development; polyamine catabolism; polyamine oxidases

DOI:  https://doi.org/10.3389/fpls.2019.00561
Carcinogenesis. 2019 May 29. pii: bgz098. [Epub ahead of print]

Polyamine synthesis enzyme AMD1 is closely associated with tumorigenesis and prognosis of human gastric cancers.

Lijiao Xu, Xue You, Qianqian Cao, Meiqin Huang, Lian-Lian Hong, Xiang-Liu Chen, Lan Lei, Zhi-Qiang Ling, Yan Chen.

  Adenosylmethionine decarboxylase 1 (AMD1) is a key enzyme involved in biosynthesis of polyamines includingspermidine and spermine. The potential function of AMD1 in human gastric cancers is unknown. We analyzed AMD1 expression level in 319 human gastric cancers samples together with the adjacent normal tissues. The protein expression level of AMD1 was significantly increased in human gastric cancer samples compared with their corresponding para-cancerous histological normal tissues (P<0.0001). The expression level of AMD1 was positively associated with Helicobactor pylori 16sRNA (P<0.0001), tumor size (P<0.0001), tumor differentiation (P<0.05), tumor venous invasion (P<0.0001), tumor lymphatic invasion (P<0.0001), blood vessel invasion (P<0.0001), and TNM stage (P<0.0001). Patients with high expression of AMD1 had a much shorter overall survival than those with normal/low expression of AMD1. Knockdown of AMD1 in human gastric cancer cells suppressed cell proliferation, colony formation and cell migration. In a tumor xenograft model, knockdown of AMD1 suppressed the tumor growth in vivo. Inhibition of AMD1 by an inhibitor SAM486A in human gastric cancer cells arrested cell cycle progression during G1-to-S transition. Collectively, our studies at the cellular, animal and human levels indicate that AMD1 has a tumorigenic effect on human gastric cancers and affect the prognosis of the patients.

Keywords:  AMD1; Polyamine; cell cycle; gastric cancer; metastasis; prognosis

DOI:  https://doi.org/10.1093/carcin/bgz098
Front Plant Sci. 2019 ;10 555

Spermidine Synthase (SPDS) Undergoes Concerted Structural Rearrangements Upon Ligand Binding - A Case Study of the Two SPDS Isoforms From Arabidopsis thaliana.

Bartosz Sekula, Zbigniew Dauter.

  Spermidine synthases (SPDSs) catalyze the production of the linear triamine, spermidine, from putrescine. They utilize decarboxylated S-adenosylmethionine (dc-SAM), a universal cofactor of aminopropyltransferases, as a donor of the aminopropyl moiety. In this work, we describe crystal structures of two SPDS isoforms from Arabidopsis thaliana (AtSPDS1 and AtSPDS2). AtSPDS1 and AtSPDS2 are dimeric enzymes that share the fold of the polyamine biosynthesis proteins. Subunits of both isoforms present the characteristic two-domain structure. Smaller, N-terminal domain is built of the two β-sheets, while the C-terminal domain has a Rossmann fold-like topology. The catalytic cleft composed of two main compartments, the dc-SAM binding site and the polyamine groove, is created independently in each AtSPDS subunits at the domain interface. We also provide the structural details about the dc-SAM binding mode and the inhibition of SPDS by a potent competitive inhibitor, cyclohexylamine (CHA). CHA occupies the polyamine binding site of AtSPDS where it is bound at the bottom of the active site with the amine group placed analogously to the substrate. The crystallographic snapshots show in detail the structural rearrangements of AtSPDS1 and AtSPDS2 that are required to stabilize ligands within the active site. The concerted movements are observed in both compartments of the catalytic cleft, where three major parts significantly change their conformation. These are (i) the neighborhood of the glycine-rich region where aminopropyl moiety of dc-SAM is bound, (ii) the very flexible gate region with helix η6, which interacts with both, the adenine moiety of dc-SAM and the bound polyamine or inhibitor, and (iii) the N-terminal β-hairpin, that limits the putrescine binding grove at the bottom of the catalytic site.

Keywords:  aminopropyltransferase; cyclohexylamine; decarboxylated S-adenosylmethionine; polyamine biosynthesis; putrescine; spermidine; spermine; triamine

DOI:  https://doi.org/10.3389/fpls.2019.00555
Cell Mol Life Sci. 2019 May 30.

Microbiome-metabolomics reveals gut microbiota associated with glycine-conjugated metabolites and polyamine metabolism in chronic kidney disease.

Ya-Long Feng, Gang Cao, Dan-Qian Chen, Nosratola D Vaziri, Lin Chen, Jun Zhang, Ming Wang, Yan Guo, Ying-Yong Zhao.

  Dysbiosis of the gut microbiome and related metabolites in chronic kidney disease (CKD) have been intimately associated with the prevalence of cardiovascular diseases. Unfortunately, thus far, there is a paucity of sufficient knowledge of gut microbiome and related metabolites on CKD progression partly due to the severely limited investigations. Using a 5/6 nephrectomized (NX) rat model, we carried out 16S rRNA sequence and untargeted metabolomic analyses to explore the relationship between colon's microbiota and serum metabolites. Marked decline in microbial diversity and richness was accompanied by significant changes in 291 serum metabolites, which were mediated by altered enzymatic activities and dysregulations of lipids, amino acids, bile acids and polyamines metabolisms. Interestingly, CCr was directly associated with some microbial genera and polyamine metabolism. However, SBP was directly related to certain microbial genera and glycine-conjugated metabolites in CKD rats. Administration of poricoic acid A (PAA) and Poria cocos (PC) ameliorated microbial dysbiosis as well as attenuated hypertension and renal fibrosis. In addition, treatments with PAA and PC lowered serum levels of microbial-derived products including glycine-conjugated compounds and polyamine metabolites. Collectively, the present study confirmed the CKD-associated gut microbial dysbiosis and identified a novel dietary and therapeutic strategy to improve the gut microbial dysbiosis and the associated metabolomic disorders and retarded the progression of kidney disease in the rat model of CKD.

Keywords:  Creatinine clearance rate; Gut microbiota; Hypertension; Metabolome; Polyamine metabolism; Renal fibrosis

DOI:  https://doi.org/10.1007/s00018-019-03155-9
Cell Rep. 2019 May 28. pii: S2211-1247(19)30676-X. [Epub ahead of print]27(9): 2798

Single-Cell Transcriptome Analysis Reveals Estrogen Signaling Coordinately Augments One-Carbon, Polyamine, and Purine Synthesis in Breast Cancer.

Detu Zhu, Zuxianglan Zhao, Guimei Cui, Shiehong Chang, Lingling Hu, Yi Xiang See, Michelle Gek Liang Lim, Dajiang Guo, Xin Chen, Barun Poudel, Paul Robson, Yumei Luo, Edwin Cheung.

DOI: https://doi.org/10.1016/j.celrep.2019.05.047
3 Biotech. 2019 Jun;9(6): 224

Characterization of a highly conserved Antheraea pernyi spermidine synthase gene.

Yi-Ren Jiang, Ting-Ting Wang, Dong-Bin Chen, Run-Xi Xia, Qun Li, Huan Wang, Yan-Qun Liu.

  In the present study, we isolated a spermidine synthase gene from Antheraea pernyi (ApSpds) using expressed sequence tag method. The obtained cDNA sequence of 1483 bp contains an open-reading frame of 864 bp encoding a polypeptide of 287 amino acids. Sequence analysis revealed that ApSpds belonged to class I of AdoMet-MTase family, and exhibited 30% identity to those from bacteria, 45-48% identity to fungi, 36-47% identity to plants, 52-54% identity to vertebrates and 53-80% identity to invertebrates. Phylogenetic analysis found that the used Spds protein sequences were well divided into five groups corresponding to bacteria, fungi, plants, invertebrates and vertebrates, respectively. These results further confirmed that Spds is highly conserved through evolution of life organisms. The ApSpds mRNA is expressed during all four developmental stages and is present in all examined tissues with the highest abundance in the muscle, in which the relative mRNA expression level was 1.6 times higher than in the fat body. Although not significant, the mRNA level decreased after high-temperature exposure suggesting that the Spds gene may not be involved in temperature stress tolerance in A. pernyi. Taken together, our results suggested that ApSpds play an important role in development of silkworm.

Keywords:  Antheraea pernyi; Evolution; Expression pattern; Spermidine synthase

DOI:  https://doi.org/10.1007/s13205-019-1762-0
Proc Natl Acad Sci U S A. 2019 May 31. pii: 201902010. [Epub ahead of print]

Arabidopsis ABCG28 is required for the apical accumulation of reactive oxygen species in growing pollen tubes.

Thanh Ha Thi Do, Hyunju Choi, Michael Palmgren, Enrico Martinoia, Jae-Ung Hwang, Youngsook Lee.

  Tip-focused accumulation of reactive oxygen species (ROS) is tightly associated with pollen tube growth and is thus critical for fertilization. However, it is unclear how tip-growing cells establish such specific ROS localization. Polyamines have been proposed to function in tip growth as precursors of the ROS, hydrogen peroxide. The ABC transporter AtABCG28 may regulate ROS status, as it contains multiple cysteine residues, a characteristic of proteins involved in ROS homeostasis. In this study, we found that AtABCG28 was specifically expressed in the mature pollen grains and pollen tubes. AtABCG28 was localized to secretory vesicles inside the pollen tube that moved toward and fused with the plasma membrane of the pollen tube tip. Knocking out AtABCG28 resulted in defective pollen tube growth, failure to localize polyamine and ROS to the growing pollen tube tip, and complete male sterility, whereas ectopic expression of this gene in root hair could recover ROS accumulation at the tip and improved the growth under high-pH conditions, which normally prevent ROS accumulation and tip growth. Together, these data suggest that AtABCG28 is critical for localizing polyamine and ROS at the growing tip. In addition, this function of AtABCG28 is likely to protect the pollen tube from the cytotoxicity of polyamine and contribute to the delivery of polyamine to the growing tip for incorporation into the expanding cell wall.

Keywords:  ABC transporters; AtABCG28; ROS; pollen tube growth; polyamine

DOI:  https://doi.org/10.1073/pnas.1902010116
Plant Cell Environ. 2019 May 27.

Photorespiratory serine hydroxymethyltransferase 1 activity impacts abiotic stress tolerance and stomatal closure.

Yanpei Liu, Caroline Mauve, Marlène Lamothe-Sibold, Florence Guérard, Nathalie Glab, Michael Hodges, Mathieu Jossier.

  The photorespiratory cycle is a crucial pathway in photosynthetic organisms since it removes toxic 2-phosphoglycolate made by the oxygenase activity of ribulose-1,5-bisphosphate carboxylase/oxygenase and retrieves its carbon as 3-phosphoglycerate. Mitochondrial serine hydroxymethyltransferase 1 (SHMT1) is an essential photorespiratory enzyme converting glycine to serine. SHMT1 regulation remains poorly understood although it could involve the phosphorylation of serine 31. Here we report the complementation of Arabidopsis thaliana shm1-1 by SHMT1 wild-type, phosphorylation mimetic (S31D) or non-phophorylatable (S31A) forms. All SHMT1 forms could almost fully complement the photorespiratory growth phenotype of shm1-1, however each transgenic line had only 50% of normal SHMT activity. In response to either a salt or drought stress, Compl-S31D lines showed a more severe growth deficiency compared to the other transgenic lines. This sensitivity to salt appeared to reflect reduced SHMT1-S31D protein amounts and a lower activity that impacted leaf metabolism leading to proline under-accumulation and over-accumulation of polyamines. The S31D mutation in SHMT1 also led to a reduction in salt-induced and ABA-induced stomatal closure. Taken together, our results highlight the importance of maintaining photorespiratory SHMT1 activity in salt and drought stress conditions and indicate that SHMT1 S31 phosphorylation could be involved in modulating SHMT1 protein stability.

Keywords:  Abiotic stress; Metabolism; Photorespiration; Protein phosphorylation; SHMT1; stomata

DOI:  https://doi.org/10.1111/pce.13595