bims-polyam 2023-04-23 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2023–04–23
six papers selected by
Sebastian J. Hofer, University of Graz

Polyamines and eIF5A hypusination facilitate SREBP2 synthesis and cholesterol production leading to enhanced enterovirus attachment and infection.
Changes in polyamine contents during Fusarium graminearum and Fusarium verticillioides inoculation in maize seedlings with or without seed-priming.
Synthesis of a fully protected long-chain polyamine subunit of aculeine B using the photoremovable NPEC group.
Metagenomes of polyamine-transforming bacterioplankton along a nearshore-open ocean transect.
The polyamine-hypusine circuit controls an oncogenic translational program essential for malignant conversion in MYC-driven lymphoma.
CX3CR1hi macrophages sustain metabolic adaptation by relieving adipose-derived stem cell senescence in visceral adipose tissue.

PLoS Pathog. 2023 Apr 18. 19(4): e1011317

Polyamines and eIF5A hypusination facilitate SREBP2 synthesis and cholesterol production leading to enhanced enterovirus attachment and infection.

Mason R Firpo, Natalie J LoMascolo, Marine J Petit, Priya S Shah, Bryan C Mounce.

Metabolism is key to cellular processes that underlie the ability of a virus to productively infect. Polyamines are small metabolites vital for many host cell processes including proliferation, transcription, and translation. Polyamine depletion also inhibits virus infection via diverse mechanisms, including inhibiting polymerase activity and viral translation. We showed that Coxsackievirus B3 (CVB3) attachment requires polyamines; however, the mechanism was unknown. Here, we report polyamines' involvement in translation, through a process called hypusination, promotes expression of cholesterol synthesis genes by supporting SREBP2 synthesis, the master transcriptional regulator of cholesterol synthesis genes. Measuring bulk transcription, we find polyamines support expression of cholesterol synthesis genes, regulated by SREBP2. Thus, polyamine depletion inhibits CVB3 by depleting cellular cholesterol. Exogenous cholesterol rescues CVB3 attachment, and mutant CVB3 resistant to polyamine depletion exhibits resistance to cholesterol perturbation. This study provides a novel link between polyamine and cholesterol homeostasis, a mechanism through which polyamines impact CVB3 infection.

DOI: https://doi.org/10.1371/journal.ppat.1011317
Biol Futur. 2023 Apr 19.

Changes in polyamine contents during Fusarium graminearum and Fusarium verticillioides inoculation in maize seedlings with or without seed-priming.

Blanka Kovács, Anett Kovács, Magda Pál, Tamás Spitkó, Csaba L Marton, Csaba Szőke.

  Maize (Zea mays L.) is the most produced field crop all over the world. One of its most critical diseases that results in economic loss is ear rot caused by various Fusarium species. Previous researches have shown that polyamines, found in all living cells, play crucial role in biotic stress responses. At the same time, biosynthesis of polyamines is of paramount importance not only for plants but also for their pathogens to promote stress tolerance and pathogenicity. In our study, we investigated the polyamine content changes induced in the seedlings of two maize genotypes of different susceptibility by isolates of Fusarium verticillioides and Fusarium graminearum, two Fusarium species of different lifestyles. Apart from that, it was examined how infection efficiency and changes in polyamine contents were modified by salicylic acid or putrescine seed soaking pre-treatments. Our observations confirmed that initial and stress-induced changes in the polyamine contents are not directly related to tolerance in either coleoptile or radicle. However, the two pathogens with different lifestyles induced remarkably distinct changes in the polyamine contents. The effect of the seed soaking pre-treatments depended on the pathogens and plant resistance as well: both salicylic acid and putrescine seed soaking had positive results against F. verticillioides, while in the case of infection with F. graminearum, seed soaking with distilled water alone affected biomass parameters positively in the tolerant genotype.

Keywords:  Fusarium graminearum; Fusarium verticillioides; Maize; Polyamine; Seed-priming

DOI:  https://doi.org/10.1007/s42977-023-00162-7
Org Biomol Chem. 2023 Apr 17.

Synthesis of a fully protected long-chain polyamine subunit of aculeine B using the photoremovable NPEC group.

Masayoshi Miyahara, Ryoya Wakabayashi, Raku Irie, Masato Oikawa.

Polyamines are ubiquitously found in nature. In this paper, we disclose our iterative coupling strategy for the synthesis of a structurally defined polymer of 1,3-propanediamine, and the polymer can be used for the synthesis of both the initially proposed structure and the revised structure of protoaculeine B isolated from a marine sponge. We first attempted the synthesis of polyamines using "the Ns strategy" but found that a polyamine with eleven Ns groups has solubility problems. We then examined the versatility of the photoremovable NPEC protecting group in polyamine synthesis. Finally, the synthesis of a suitably protected 12-mer polyamine was achieved employing the NPEC group for the temporary protection of a terminal amino group.

DOI: https://doi.org/10.1039/d3ob00369h
Mar Life Sci Technol. 2022 May;4(2): 268-276

Metagenomes of polyamine-transforming bacterioplankton along a nearshore-open ocean transect.

Xinxin Lu, Kai Wang, Xiaozhen Mou.

  Short-chained aliphatic polyamines (PAs) have recently been recognized as an important carbon, nitrogen, and/or energy source for marine bacterioplankton. To study the genes and taxa involved in the transformations of different PA compounds and their potential variations among marine systems, we collected surface bacterioplankton from nearshore, offshore, and open ocean stations in the Gulf of Mexico and examined their metagenomic responses to additions of single PA model compounds (putrescine, spermidine, or spermine). Genes affiliated with PA uptake and all three known PA degradation pathways, i.e., transamination, γ-glutamylation, and spermidine cleavage, were significantly enriched in most PA-treated metagenomes. In addition, identified PA-transforming taxa were mostly the alpha and gamma classes of Proteobacteria, with less important contributions from members of Betaproteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria, Firmicutes, and Planctomycetes. These findings suggest that PA transformations are ubiquitous, have diverse pathways, and are carried out by a broad range of the bacterioplankton taxa in the Gulf of Mexico. Identified PA-transforming bacterial genes and taxa were different among nearshore, offshore, and open ocean sites, but were little different among individual compound-amended metagenomes at any specific site. These observations further indicate that PA-transforming taxa and genes are site-specific and with high similarities among PA compounds.
Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-021-00114-x.

Keywords:  Microbial transformation; Polyamines; Putrescine; Spermidine; Spermine

DOI:  https://doi.org/10.1007/s42995-021-00114-x
Blood Cancer Discov. 2023 Apr 18. pii: BCD-22-0162. [Epub ahead of print]

The polyamine-hypusine circuit controls an oncogenic translational program essential for malignant conversion in MYC-driven lymphoma.

Shima Nakanishi, Jiannong Li, Anders E Berglund, Youngchul Kim, Yonghong Zhang, Ling Zhang, Chunying Yang, Jinming Song, Raghavendra G Mirmira, John L Cleveland.

The MYC oncoprotein is activated in a broad spectrum of human malignancies and transcriptionally reprograms the genome to drive cancer cell growth. Given this, it is unclear if targeting a single effector of MYC will have therapeutic benefit. MYC activates the polyamine-hypusine circuit, which post-translationally modifies the eukaryotic translation factor eIF5A. The roles of this circuit in cancer are unclear. Here we report essential intrinsic roles for hypusinated eIF5A in the development and maintenance of MYC-driven lymphoma, where loss of eIF5A hypusination abolishes malignant transformation of MYC-overexpressing B cells. Mechanistically, integrating RNA-seq, Ribo-seq and proteomic analyses revealed that efficient translation of select targets is dependent upon eIF5A hypusination, including regulators of G1-to-S phase cell cycle progression and DNA replication. This circuit thus controls MYC's proliferative response, and it is also activated across multiple malignancies. These findings suggest the hypusine circuit as a therapeutic target for several human tumor types.

DOI: https://doi.org/10.1158/2643-3230.BCD-22-0162
Cell Rep. 2023 Apr 20. pii: S2211-1247(23)00435-7. [Epub ahead of print]42(5): 112424

CX3CR1hi macrophages sustain metabolic adaptation by relieving adipose-derived stem cell senescence in visceral adipose tissue.

Zixin Zhou, Huiying Zhang, Yan Tao, Haipeng Jie, Jingyuan Zhao, Jinhao Zang, Huijie Li, Yalin Wang, Tianci Wang, Hui Zhao, Yuan Li, Chun Guo, Faliang Zhu, Haiting Mao, Lining Zhang, Fengming Liu, Qun Wang.

  Adipose-derived stem cells (ASCs) drive healthy visceral adipose tissue (VAT) expansion via adipocyte hyperplasia. Obesity induces ASC senescence that causes VAT dysfunction and metabolic disorders. It is challenging to restrain this process by biological intervention, as mechanisms of controlling VAT ASC senescence remain unclear. We demonstrate that a population of CX3CR1hi macrophages is maintained in mouse VAT during short-term energy surplus, which sustains ASCs by restraining their senescence, driving adaptive VAT expansion and metabolic health. Long-term overnutrition induces diminishment of CX3CR1hi macrophages in mouse VAT accompanied by ASC senescence and exhaustion, while transferring CX3CR1hi macrophages restores ASC reservoir and triggers VAT beiging to alleviate the metabolic maladaptation. Mechanistically, visceral ASCs attract macrophages via MCP-1 and shape their CX3CR1hi phenotype via exosomes; these macrophages relieve ASC senescence by promoting the arginase1-eIF5A hypusination axis. These findings identify VAT CX3CR1hi macrophages as ASC supporters and unravel their therapeutic potential for metabolic maladaptation to obesity.

Keywords:  CP: Immunology; CP: Metabolism; CX3CR1; adipose-derived stem cell; cellular senescence; macrophage; obesity; visceral adipose tissue

DOI:  https://doi.org/10.1016/j.celrep.2023.112424