bims-polyam 2022-09-04 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2022–09–04
eight papers selected by
Sebastian J. Hofer, University of Graz

Spermine-mediated metabolic homeostasis improves growth and stress tolerance in creeping bentgrass (Agrostis stolonifera) under water or high-temperature stress.
Interrogation of T Cell-Enriched Tumors Reveals Prognostic and Immunotherapeutic Implications of Polyamine Metabolism.
Singlet Molecular Oxygen Generation in the Reaction of Biological Haloamines of Amino Acids and Polyamines with Hydrogen Peroxide.
Microbiome dysbiosis inhibits carcinogen-induced murine oral tumorigenesis.
Spermidine alleviates oxidative damage and enhances phenolic compounds accumulation in barley seedlings under UV-B stress.
Application of Artificial Intelligence to Plasma Metabolomics Profiles to Predict Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.
Arginine metabolism regulates the pathogenesis of inflammatory bowel disease.
Label-free protocol to quantify protein affinity using isothermal titration calorimetry and bio-layer interferometry of a human eIF5-mimic protein.

Front Plant Sci. 2022 ;13 944358

Spermine-mediated metabolic homeostasis improves growth and stress tolerance in creeping bentgrass (Agrostis stolonifera) under water or high-temperature stress.

Zhou Li, Bizhen Cheng, Xing Wu, Yan Zhang, Guangyan Feng, Yan Peng.

  Plants have developed diverse defense strategies to reduce the detrimental effects of a wide range of environmental stresses. The objectives of this study were to explore the function of spermine (Spm) on mediating growth and physiological changes in water homeostasis, photosynthetic performance, and oxidative damage and to further examine the regulatory mechanism of Spm on global metabolites reprogramming and associated metabolic pathways in horticultural creeping bentgrass (Agrostis stolonifera) under water and heat stresses. The 21-days-old plants were pretreated with or without 100 μM Spm for 3 days and then subjected to water stress (17% polyethylene glycol 6000), high-temperature stress (40/35°C, day/night), or normal condition (control without water stress and heat stress) for 18 days. Results demonstrated that exogenous application of Spm could significantly increase endogenous polyamine (PAs), putrescine (Put), spermidine (Spd), and Spm contents, followed by effective alleviation of growth retardant, water imbalance, photoinhibition, and oxidative damage induced by water and heat stress. Metabolites' profiling showed that a total of 61 metabolites were differentially or commonly regulated by Spm in leaves. Spm upregulated the accumulation of mannose, maltose, galactose, and urea in relation to enhanced osmotic adjustment (OA), antioxidant capacity, and nitrogen metabolism for growth maintenance under water and heat stress. Under water stress, Spm mainly induced the accumulation of sugars (glucose-1-phosphate, sucrose-6-phosphate, fructose, kestose, maltotriose, and xylose), amino acids (glutamic acid, methionine, serine, and threonine), and organic acids (pyruvic acid, aconitic acid, and ketoglutaric acid) involved in the respiratory pathway and myo-inositol associated with energy production, the ROS-scavenging system, and signal transduction. In response to heat stress, the accumulation of alanine, glycine, gallic acid, malic acid, or nicotinic acid was specifically enhanced by Spm contributing to improvements in antioxidant potency and metabolic homeostasis. This study provides novel evidence of Spm-induced,tolerance to water and heat stresses associated with global metabolites reprogramming in favor of growth maintenance and physiological responses in horticultural plants.

Keywords:  abiotic stress; metabolic pathways; metabolites; osmotic adjustment (OA); polyamine (PA); signal transduction

DOI:  https://doi.org/10.3389/fpls.2022.944358
Cancer Res Commun. 2022 Jul;2(7): 639-652

Interrogation of T Cell-Enriched Tumors Reveals Prognostic and Immunotherapeutic Implications of Polyamine Metabolism.

R Alex Harbison, Rajeev Pandey, Michael Considine, Robert D Leone, Tracy Murray-Stewart, Rossin Erbe, Raj Mandal, Mark Burns, Robert A Casero, Tanguy Seiwert, Carole Fakhry, Drew Pardoll, Elana Fertig, Jonathan D Powell.

  Metabolic features of the tumor microenvironment (TME) antagonize anti-tumor immunity. We hypothesized that T cell infiltrated tumors with a known antigen should exhibit superior clinical outcomes, though some fare worse given unfavorable metabolic features leveraging T cell-infiltrated (Thi), human papillomavirus-related (HPV+) head and neck squamous cell carcinomas (HNSC) to test this hypothesis. Expression of 2,520 metabolic genes were analyzed among Thi HPV+ HNSCs stratified by high-risk molecular subtype. RNAseq data from The Cancer Genome Atlas (TCGA; 10 cancer types), single cell RNAseq data, and an immunotherapy-treated melanoma cohort were used to test the association between metabolic gene expression and clinical outcomes and contribution of tumor versus stromal cells to metabolic gene expression. Polyamine (PA) metabolism genes were overexpressed in high-risk, Thi HPV+ HNSCs. Genes involved in PA biosynthesis and transport were associated with T cell infiltration, recurrent or persistent cancer, overall survival status, primary site, molecular subtype, and MYC genomic alterations. PA biogenesis gene sets were associated with tumor intrinsic features while myeloid cells in HPV+ HNSCs were enriched in PA catabolism, regulatory, transport, putrescine, and spermidine gene set expression. PA gene set expression also correlated with IFNγ or cytotoxic T cell ssGSEA scores across TCGA tumor types. PA transport ssGSEA scores were associated with poor survival whereas putrescine ssGSEA scores portended better survival for several tumor types. Thi melanomas enriched in PA synthesis or combined gene set expression exhibited worse anti-PD-1 responses. These data address hurdles to anti-tumor immunity warranting further investigation of divergent polyamine metabolism in the TME.

Keywords:  Human papillomavirus; head and neck cancer; immunometabolism; polyamines

DOI:  https://doi.org/10.1158/2767-9764.crc-22-0061
Photochem Photobiol. 2022 Sep 01.

Singlet Molecular Oxygen Generation in the Reaction of Biological Haloamines of Amino Acids and Polyamines with Hydrogen Peroxide.

Rafaela Oliveira Nascimento, Fernanda Manso Prado, Marisa Helena Gennari de Medeiros, Graziella Eliza Ronsein, Paolo Di Mascio.

  Leucocytes generate hypohalous acids (HOCl and HOBr) to defend against pathogens. In cells, hypohalous acids react with amine-containing molecules, such as amino acids and polyamines, producing chloramines and bromamines, reservoirs of oxidizing power that can potentially damage host tissues at sites of inflammation. Hypohalous acids also react with H2 O2 to produce stoichiometric amounts of singlet molecular oxygen (1 O2 ), but its generation in leucocytes is still under debate. Additionally, it is unclear if haloamines generate 1 O2 following a reaction with H2 O2 . Herein, we provide evidence of the generation of 1 O2 in the reactions between amino acid-derived (taurine, N-α-acetyl-Lysine, and glycine) and polyamine-derived (spermine and spermidine) haloamines and H2 O2 in an aqueous solution. The unequivocal formation of 1 O2 was detected by monitoring its characteristic monomol light emission at 1270 nm in the near-infrared region. For amino acid-derived haloamines, the presence of 1 O2 was further confirmed by chemical trapping with anthracene-9,10-divinylsulfonate and HPLC-MS/MS detection. Altogether, photoemission and chemical trapping studies demonstrated that chloramines were less effective at producing 1 O2 than bromamines of amino acids and polyamines. Thus, 1 O2 formation via bromamines and H2 O2 may be a potential source of 1 O2 in non-illuminated biological systems.

Keywords:  Bromamines; Chloramines; Hydrogen peroxide; Hypohalous acids; Singlet Molecular Oxygen

DOI:  https://doi.org/10.1111/php.13708
J Cancer. 2022 ;13(10): 3051-3060

Microbiome dysbiosis inhibits carcinogen-induced murine oral tumorigenesis.

Yuh-Ling Chen, Kuan-Chih Huang, Jer-Horng Wu, Tsunglin Liu, Jiung-Wen Chen, Jia-Yan Xie, Meng-Yen Chen, Li-Wha Wu, Chun-Liang Tung.

  Oral cancer is one of the most common cancers worldwide and ranks fourth for the mortality rate of cancers in males in Taiwan. The oral microbiota is the microbial community in the oral cavity, which is essential for maintaining oral health, but the relationship between oral tumorigenesis and the oral microbiota remains to be clarified. This study evaluated the effect of microbiome dysbiosis on oral carcinogenesis in mice, and the impact of the microbiome and its metabolic pathways on regulating oral carcinogenesis. We found that antibiotics treatment decreases carcinogen-induced oral epithelial malignant transformation. Microbiome analysis based on 16S rRNA gene sequencing revealed that the species richness of fecal specimens was significantly reduced in antibiotic-treated mice, while that in the salivary specimens was not decreased accordingly. Differences in bacterial composition, including Lactobacillus animalis abundance, in the salivary samples of cancer-bearing mice was dramatically decreased. L. animalis was the bacterial species that increased the most in the saliva of antibiotic-treated mice, suggesting that L. animalis may be negatively associated with oral carcinogenesis. In functional analysis, the microbiome in the saliva of the tumor-bearing group showed greater potential for polyamine biosynthesis. Immunochemical staining proved that spermine oxidase, an effective polyamine oxidase, was upregulated in mouse oral cancer lesions. In conclusion, oral microbiome dysbiosis may alter polyamine metabolic pathways and reduce carcinogen-induced malignant transformation of the oral epithelium.

Keywords:  antibiotics-induced microbiome dysbiosis; microbiota; oral cancer; polyamine; spermine oxidase

DOI:  https://doi.org/10.7150/jca.75947
J Sci Food Agric. 2022 Aug 14.

Spermidine alleviates oxidative damage and enhances phenolic compounds accumulation in barley seedlings under UV-B stress.

Chong Xie, Pei Wang, Zhenxin Gu, Runqiang Yang.

   BACKGROUND: Ultraviolet B (UV-B) radiation can enhance the accumulation of phenolic compounds (PCs) in barley seedling, although this may result in severe oxidative damage. In the present study, the role of spermidine in alleviating oxidative damage and regulating synthesis of PCs in barley seedlings under UV-B stress was investigated.
RESULTS: Exogenous spermidine increased the length and fresh weight as well as PCs contents of barley seedlings under UV-B stress. Application of dicyclohexylamine, an inhibitor of endogenous spermidine synthesis, significantly inhibited the growth and PC accumulation of barley seedlings under UV-B stress, although this inhibitory effect can be alleviated by exogenous spermidine. Exogenous spermidine increased the contents of vanillic acid, syringic acid, protocatechuic acid and p-coumaric acid in barley seedlings under UV-B stress by 20-200% through enhancing the activities of enzymes related to synthesis of these acids. In addition, exogenous spermidine enhanced activities and gene expression of antioxidant enzymes in barley seedlings under UV-B stress, including peroxidase, glutathione reductase and glutathione S-transferase.
CONCLUSION: Spermidine can alleviate oxidative damage of barley seedlings under UV-B stress and enhance the accumulation of PCs. © 2022 Society of Chemical Industry.

Keywords:  UV-B; antioxidant capacity; barley seedling; phenolic compounds; spermidine

DOI:  https://doi.org/10.1002/jsfa.12176
Front Artif Intell. 2022 ;5 876100

Application of Artificial Intelligence to Plasma Metabolomics Profiles to Predict Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

Ehsan Irajizad, Ranran Wu, Jody Vykoukal, Eunice Murage, Rachelle Spencer, Jennifer B Dennison, Stacy Moulder, Elizabeth Ravenberg, Bora Lim, Jennifer Litton, Debu Tripathym, Vicente Valero, Senthil Damodaran, Gaiane M Rauch, Beatriz Adrada, Rosalind Candelaria, Jason B White, Abenaa Brewster, Banu Arun, James P Long, Kim Anh Do, Sam Hanash, Johannes F Fahrmann.

  There is a need to identify biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are less likely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied artificial intelligence to comprehensive metabolic profiles to identify additional metabolites associated with treatment response. Using a deep learning model (DLM), a metabolite panel consisting of two polyamines as well as nine additional metabolites was developed for improved prediction of RCB-II/III. The DLM has potential clinical value for identifying TNBC patients who are unlikely to respond to NACT and who may benefit from other treatment modalities.

Keywords:  artificial intelligence; biomarkers; deep-learning model; neoadjuvant chemotherapy; prediction; triple-negative breast cancer

DOI:  https://doi.org/10.3389/frai.2022.876100
Nutr Rev. 2022 Aug 30. pii: nuac070. [Epub ahead of print]

Arginine metabolism regulates the pathogenesis of inflammatory bowel disease.

Jun-Yi Li, Yan-Chao Guo, Hai-Feng Zhou, Tian-Tian Yue, Fa-Xi Wang, Fei Sun, Wen-Zhu Wang.

  The pathogenesis of inflammatory bowel disease (IBD) is related to genetic susceptibility, enteric dysbiosis, and uncontrolled, chronic inflammatory responses that lead to colonic tissue damage and impaired intestinal absorption. As a consequence, patients with IBD are prone to nutrition deficits after each episode of disease resurgence. Nutritional supplementation, especially for protein components, is often implemented during the remission phase of IBD. Notably, ingested nutrients could affect the progression of IBD and the prognostic outcome of patients; therefore, they should be cautiously evaluated prior to being used for IBD intervention. Arginine (Arg) is a semi-essential amino acid required for protein synthesis and intimately associated with gut pathophysiology. To help optimize arginine-based nutritional intervention strategies, the present work summarizes that during the process of IBD, patients manifest colonic Arg deficiency and the turbulence of Arg metabolic pathways. The roles of Arg-nitric oxide (catalyzed by inducible nitric oxide synthase) and Arg-urea (catalyzed by arginases) pathways in IBD are debatable; the Arg-polyamine and Arg-creatine pathways are mainly protective. Overall, supplementation with Arg is a promising therapeutic strategy for IBD; however, the dosage of Arg may need to be carefully tailored for different individuals at different disease stages. Additionally, the combination of Arg supplementation with inhibitors of Arg metabolic pathways as well as other treatment options is worthy of further exploration.

Keywords:  arginine metabolism; arginine supplementation; arginine uptake; inflammatory bowel disease

DOI:  https://doi.org/10.1093/nutrit/nuac070
STAR Protoc. 2022 Sep 16. 3(3): 101615

Label-free protocol to quantify protein affinity using isothermal titration calorimetry and bio-layer interferometry of a human eIF5-mimic protein.

Chingakham Ranjit Singh, Rahul Jaiswal, Carlos R Escalante, Katsura Asano.

  eIF5-mimic protein (5MP) controls translation through its interaction with eukaryotic translation initiation factor (eIF) 2 and eIF3 and alters non-AUG translation rates for oncogenes in cancer and repeat expansions in neurodegenerative disease. To precisely evaluate the effect of 5MP mutations on binding affinity against eIFs, here we describe two label-free protocols of affinity measurement for 5MP binding to eIF2 or eIF3 protein segments, termed isothermal titration calorimetry (ITC) and bio-layer interferometry (BLI), starting with how to purify proteins used. For complete details on the use and execution of this protocol, please refer to Singh et al. (2021).

Keywords:  Biophysics; Molecular biology

DOI:  https://doi.org/10.1016/j.xpro.2022.101615