bims-polyam 2021-10-24 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–10–24
ten papers selected by
Sebastian J. Hofer, University of Graz

Maternal mosaicism for a missense variant in the SMS gene that causes Snyder-Robinson syndrome.
Targeting Cardiovascular Risk Factors Through Dietary Adaptations and Caloric Restriction Mimetics.
The Effect of Impaired Polyamine Transport on Pneumococcal Transcriptome.
Spermidine Induces Expression of Stress Associated Proteins (SAPs) Genes and Protects Rice Seed from Heat Stress-Induced Damage during Grain-Filling.
CsCDPK6, a CsSAMS1-Interacting Protein, Affects Polyamine/Ethylene Biosynthesis in Cucumber and Enhances Salt Tolerance by Overexpression in Tobacco.
Quantification of Biogenic Amines in 35 Korean Cottage Industry Traditional Gochujang (Fermented Red Pepper Paste) Products.
Contents of Polyamines and Biogenic Amines in Canned Pet (Dogs and Cats) Food on the Austrian Market.
Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis.
Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction.
Aqueous metabolome of tissue-specific conditional Pten-knockout mouse prostate cancer and TRAMP neuroendocrine carcinoma.

Cold Spring Harb Mol Case Stud. 2021 Oct 19. pii: mcs.a006122. [Epub ahead of print]

Maternal mosaicism for a missense variant in the SMS gene that causes Snyder-Robinson syndrome.

Mohammad Marhabaie, Scott E Hickey, Katherine E Miller, Olivia Grischow, Kathleen M Schieffer, Samuel J Franklin, David M Gordon, Samantha Choi, Theresa Mihalic Mosher, Peter White, Daniel C Koboldt, Richard K Wilson.

  There is increasing recognition for the contribution of genetic mosaicism to human disease, particularly as high-throughput sequencing has enabled detection of sequence variants at very low allele frequencies. Here, we describe an infant male who presented at 9 months of age with hypotonia, dysmorphic features, congenital heart disease, hyperinsulinemic hypoglycemia, hypothyroidism, and bilateral sensorineural hearing loss. Whole-genome sequencing of the proband and the parents uncovered an apparent de novo mutation in the X-linked SMS gene. SMS encodes spermine synthase, which catalyzes the production of spermine from spermidine. Inactivation of the SMS gene disrupts the spermidine/spermine ratio, resulting in Snyder-Robinson syndrome. The variant in our patient is absent from the gnomAD and ExAC databases and causes a missense change (p.Arg130Cys) predicted to be damaging by most in silico tools. While Sanger sequencing confirmed the de novo status in our proband, PCR and deep targeted resequencing to ~84,000-175,000x depth revealed that the variant is present in blood from the unaffected mother at ~3% variant allele frequency. Our findings thus provided a long-sought diagnosis for the family while highlighting the role of parental mosaicism in severe genetic disorders.

Keywords:  Bilateral sensorineural hearing impairment; Congenital hypothyroidism; Defect in the atrial septum; Hyperinsulinemic hypoglycemia; Severe muscular hypotonia

DOI:  https://doi.org/10.1101/mcs.a006122
Front Nutr. 2021 ;8 758058

Targeting Cardiovascular Risk Factors Through Dietary Adaptations and Caloric Restriction Mimetics.

Julia Voglhuber, Senka Ljubojevic-Holzer, Mahmoud Abdellatif, Simon Sedej.

  The average human life expectancy continues to rise globally and so does the prevalence and absolute burden of cardiovascular disease. Dietary restriction promotes longevity and improves various cardiovascular risk factors, including hypertension, obesity, diabetes mellitus, and metabolic syndrome. However, low adherence to caloric restriction renders this stringent dietary intervention challenging to adopt as a standard practice for cardiovascular disease prevention. Hence, alternative eating patterns and strategies that recapitulate the salutary benefits of caloric restriction are under intense investigation. Here, we first provide an overview of alternative interventions, including intermittent fasting, alternate-day fasting and the Mediterranean diet, along with their cardiometabolic effects in animal models and humans. We then present emerging pharmacological alternatives, including spermidine, NAD+ precursors, resveratrol, and metformin, as promising caloric restriction mimetics, and briefly touch on the mechanisms underpinning their cardiometabolic and health-promoting effects. We conclude that implementation of feasible dietary approaches holds the promise to attenuate the burden of cardiovascular disease and facilitate healthy aging in humans.

Keywords:  autophagy; caloric restriction; caloric restriction mimetics; cardiovascular risk factors; dietary regimens; hypertension; intermittent fasting; obesity

DOI:  https://doi.org/10.3389/fnut.2021.758058
Pathogens. 2021 Oct 14. pii: 1322. [Epub ahead of print]10(10):

The Effect of Impaired Polyamine Transport on Pneumococcal Transcriptome.

Mary F Nakamya, Moses B Ayoola, Leslie A Shack, Edwin Swiatlo, Bindu Nanduri.

  Infections due to Streptococcus pneumoniae, a commensal in the nasopharynx, still claim a significant number of lives worldwide. Genome plasticity, antibiotic resistance, and limited serotype coverage of the available polysaccharide-based conjugate vaccines confounds therapeutic interventions to limit the spread of this pathogen. Pathogenic mechanisms that allow successful adaption and persistence in the host could be potential innovative therapeutic targets. Polyamines are ubiquitous polycationic molecules that regulate many cellular processes. We previously reported that deletion of polyamine transport operon potABCD, which encodes a putrescine/spermidine transporter (ΔpotABCD), resulted in an unencapsulated attenuated phenotype. Here, we characterize the transcriptome, metabolome, and stress responses of polyamine transport-deficient S. pneumoniae. Compared with the wild-type strain, the expression of genes involved in oxidative stress responses and the nucleotide sugar metabolism was reduced, while expression of genes involved in the Leloir, tagatose, and pentose phosphate pathways was higher in ΔpotABCD. A metabolic shift towards the pentose phosphate pathway will limit the synthesis of precursors of capsule polysaccharides. Metabolomics results show reduced levels of glutathione and pyruvate in the mutant. Our results also show that the potABCD operon protects pneumococci against hydrogen peroxide and nitrosative stress. Our findings demonstrate the importance of polyamine transport in pneumococcal physiology that could impact in vivo fitness. Thus, polyamine transport in pneumococci represents a novel target for therapeutic interventions.

Keywords:  Streptococcus pneumoniae; metabolome; nitrosative stress; oxidative stress; polyamine transporter; transcriptome

DOI:  https://doi.org/10.3390/pathogens10101322
Antioxidants (Basel). 2021 Sep 28. pii: 1544. [Epub ahead of print]10(10):

Spermidine Induces Expression of Stress Associated Proteins (SAPs) Genes and Protects Rice Seed from Heat Stress-Induced Damage during Grain-Filling.

Min Chen, Yuying Fu, Qingshan Mou, Jianyu An, Xiaobo Zhu, Temoor Ahmed, Sheng Zhang, Farwa Basit, Jin Hu, Yajing Guan.

  Heat stress during seed maturation significantly reduced seed size and quality. Polyamines, especially spermidine (Spd), were reported to be closely related to seed development and plant heat tolerance. Stress-associated proteins (SAPs) also played a critical role in plant heat resistance, but the relationship between Spd and SAPs in improving rice tolerance to heat stress during grain filling has not been reported. Our results showed that the external spraying Spd (1.5 mM) significantly increased seed germination rate, germination index, vigor index and 1000-grain weight, significantly increased endogenous Spd, spermine (Spm) content and peroxidase activity; significantly reduced MDA content; and greatly alleviated the impact of heat stress on rice seed quality during grain filling stage as compared with high temperature control. OsSAP5 was the most upregulated expression induced by Spd, and may be mainly involved in the Spd-mediated enhancement of high-temperature resistance during rice seed development. Overexpression of OsSAP5 in Arabidopsis enhanced 1000-grain weight and seed heat resistance. Exogenous Spd alleviated the survival rate and seedling length, reduced MDA content, and upregulated the expression levels of SPDS and SPMS in Atsap4 mutant under high temperature during seed germination. In all, exogenous Spd alleviated the heat damage on seed quality during the grain filling stage and seed germination stage by improving endogenous Spd and Spm. OsSAP5, a key gene induced by Spd, might be involved in the rice heat resistance and seed quality in coordination with Spd and Spm.

Keywords:  high-temperature; seed quality; spermidine; stress-associated proteins; thermotolerance

DOI:  https://doi.org/10.3390/antiox10101544
Int J Mol Sci. 2021 Oct 15. pii: 11133. [Epub ahead of print]22(20):

CsCDPK6, a CsSAMS1-Interacting Protein, Affects Polyamine/Ethylene Biosynthesis in Cucumber and Enhances Salt Tolerance by Overexpression in Tobacco.

Heyuan Zhu, Meiwen He, Mohammad Shah Jahan, Jianqiang Wu, Qinsheng Gu, Sheng Shu, Jin Sun, Shirong Guo.

  S-adenosylmethionine synthetase (SAMS) plays a crucial role in regulating stress responses. In a recent study, we found that overexpression of the cucumber gene CsSAMS1 in tobacco can affect the production of polyamines and ethylene, as well as enhancing the salt stress tolerance of tobacco, but the exact underlying mechanisms are elusive. The calcium-dependent protein kinase (CDPK) family is ubiquitous in plants and performs different biological functions in plant development and response to abiotic stress. We used a yeast two-hybrid system to detect whether the protein CDPK6 could interact with SAMS1 and verified their interaction by bimolecular fluorescence complementation (BiFC) and co-immunoprecipitation (Co-IP) assays. To further explore the function of cucumber CDPK6, we isolated and characterized CsCDPK6 in cucumber. CsCDPK6 is a membrane protein that is highly expressed under various abiotic stresses, including salt stress. It was also observed that ectopic overexpression of CsCDPK6 in tobacco enhanced salt tolerance. Under salt stress, CsCDPK6-overexpressing lines enhanced the survival rate and reduced stomatal apertures in comparison to wild-type (WT) lines, as well as lowering malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents and causing less relative electrolyte leakage. Moreover, repression of CsCDPK6 expression by virus-induced gene silencing (VIGS) in cucumber seedling cotyledons under salt stress increased ethylene production and promoted the transformation from putrescine (Put) to spermidine (Spd) and spermine (Spm). These findings shed light on the interaction of CsSAMS1 and CsCDPK6, which functions positively to regulate salt stress in plants.

Keywords:  PA/ethylene metabolism; S-adenosylmethionine synthetase (SAMS); calcium-dependent protein kinase; cucumber; salt stress

DOI:  https://doi.org/10.3390/ijms222011133
Foods. 2021 Oct 06. pii: 2370. [Epub ahead of print]10(10):

Quantification of Biogenic Amines in 35 Korean Cottage Industry Traditional Gochujang (Fermented Red Pepper Paste) Products.

Srinivasan Ramalingam, Ashutosh Bahuguna, SeMi Lim, Ah-Ryeong Joe, Jong-Suk Lee, So-Young Kim, Myunghee Kim.

  Traditional gochujang is well known for its distinguished flavor and taste. However, the safety of cottage industry gochujang products is uncertain, particularly, in terms of biogenic amine (BA) content which is not yet documented. The present study aimed to determine the level of BAs present in 35 traditional gochujang products nationwide. All gochujang products had considerable amounts of total BAs ranging from 52.95 mg/kg to 176.24 mg/kg. Individually, histamine and tyramine were either not detected or detected up to 16.94 mg/kg and 2.15-52.34 mg/kg, respectively. In all the tested gochujang products, putrescine, spermidine, and spermine were detected in the range of 7.60-56.72 mg/kg, 14.96-36.93 mg/kg, and 4.68-16.31 mg/kg, respectively. A total of 22 and 19 gochujang products had less than 1 mg/kg of cadaverine and histamine, respectively. The findings indicate that all the gochujang products tested herein had BA levels below the suggested toxicity limits recommended by the various regulatory authorities, which reveal that they are safe for human consumption.

Keywords:  HPLC; fermentation; food safety; histamine; principal component analysis; putrescine; red pepper paste

DOI:  https://doi.org/10.3390/foods10102370
Foods. 2021 Oct 05. pii: 2365. [Epub ahead of print]10(10):

Contents of Polyamines and Biogenic Amines in Canned Pet (Dogs and Cats) Food on the Austrian Market.

Peter Paulsen, Susanne Bauer, Friedrich Bauer, Zuzana Dicakova.

  Biogenic amines accumulate in proteinaceous raw materials used for pet food production. In canned, sterilized food, amine levels of the ingredients are preserved and may both be indicative of hygiene deficiencies in the ingredients as well as for potential adverse effects to the animals feeding on it. We determined the contents of biogenic amines and polyamines (dansyl derivatives, high performance liquid chromatography) in a variety of canned food for dogs (n = 72) and cats (n = 114) on the Austrian market and compared the results with common quality indices. Contents of putrescine, cadaverine, and tyramine were below the limit of detection in >70% of samples (maximum values: 21.5, 98.4 and 32.5 mg/kg wet weight, respectively). Median contents of histamine, spermidine, and spermine were 14.5, 12.7, and 29.4 mg/kg, and maximum values were 61.6, 28.2, and 53.6 mg/kg wet weight, respectively. The sum of (putrescine + cadaverine + histamine + tyramine) was >50 mg/kg in 22.6% of samples. The biogenic amine index exceeded "1" in 26.7% of samples. Whilst cat food contained significantly higher amounts of tyramine, dog food contained significantly higher amounts of histamine and spermine. In canned cat food, the ingredient "fish" was identified as a statistically significant risk factor for a biogenic amine index > 1 (relative risk = 3.0 (95% confidence interval: 1.8-5.5)) and for (putrescine + cadaverine + histamine + tyramine) exceeding 50 mg/kg (relative risk = 2.4 (95% confidence interval: 1.2-4.6)), due to higher contents of cadaverine in food samples containing fish. While all samples met the limits suggested in pet food production, we could demonstrate that the inclusion of fish in the formulation bears a significant risk for higher cadaverine contents.

Keywords:  amines; biogenic amine index; canned pet food; fish

DOI:  https://doi.org/10.3390/foods10102365
Neurol Sci. 2021 Oct 22.

Study of arginine metabolism in medication overuse chronic migraine: possible defect in NO synthesis.

Giovanni D'Andrea, Antonina Gucciardi, Giuseppe Giordano, Gennaro Bussone, Alberta Leon.

   BACKGROUND AND AIM: The pathogenesis of the pain that occurs in episodic migraine attack is due to the activation of the trigeminal system's first neuron receptors located on vessel wall. The release from the endothelium of nitric oxide, a product of arginine metabolism, causes vasodilation and stretching of the vascular trigeminal system and promotes pain. It is unknown whether this same metabolic event is involved in the pain accompanying chronic migraine. To understand the possible role of arginine in the pathogenesis of chronic migraine patients, we evaluated the metabolism of arginine in plasma of chronic migraine and control subjects.
METHODS: We evaluated the metabolism of arginine in a group of patients affected by chronic migraine. Quantification of arginine, ornithine, citrulline, monomethyl arginine (NMMA), dimethylarginines (ADMA, SDMA), and tyramine was performed by ultra-performance liquid chromatography coupled with a triple quadrupole mass spectrometer.
RESULTS: Chronic migraine patients showed low plasma levels of arginine, significantly elevated levels of ornithine, ADMA, and NMMA whereas the levels of citrulline and SDMA were in the range of controls.
CONCLUSIONS: The elevated levels of ADMA and NMMA, inhibitors of nitric oxide synthase, suggest that the metabolism of arginine may be inhibited with a possible reduction of NO release in the circulation of chronic patients. This suggests that the origin of pain may not be related to the vasodilation of trigeminal vascular system that occurs in episodic migraine patients.

Keywords:  ADMA; Arginine; Migraine; Tyramine

DOI:  https://doi.org/10.1007/s10072-021-05672-7
Sci Rep. 2021 Oct 19. 11(1): 20684

Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction.

Petra Büttner, Sarah Werner, Svetlana Baskal, Dimitrios Tsikas, Volker Adams, Philipp Lurz, Christian Besler, Sarah Knauth, Martin Bahls, Edzard Schwedhelm, Holger Thiele.

Endothelial dysfunction and altered nitric oxide (NO) metabolism are considered causal factors in heart failure with preserved ejection fraction (HFpEF). NO synthase activity depends on the availability of arginine and its derivatives. Thus, we analyzed arginine, associated metabolites, arginine-metabolizing enzymes and NO turnover in 20-week-old female healthy lean (L-ZSF1) and obese ZSF1 rats (O-ZSF1) with HFpEF. Serum, urine and lysates of liver, kidney and heart were analyzed. There were significantly lower lysine (- 28%), arginine (- 31%), homoarginine (- 72%) and nitrite (- 32%) levels in serum of O-ZSF1 rats. Ornithine (+ 60%) and citrulline (+ 20%) levels were higher. Similar results were found in the heart. Expression of arginine consuming enzymes in liver and kidney was unchanged. Instead, we observed a 5.8-fold higher arginase 1 expression, presumably of granulocyte origin, in serum and > fourfold increased cardiac macrophage invasion in O-ZSF1. We conclude that inflammatory cells in blood and heart consume arginine and probably homoarginine via arginase 1 and inducible NO synthase and release ornithine and citrulline. In combination with evidence for decreased NO turnover in O-ZSF1 rats, we assume lower arginine bioavailability to endothelial NO synthase.

DOI: https://doi.org/10.1038/s41598-021-00216-7
Prostate. 2021 Oct 18.

Aqueous metabolome of tissue-specific conditional Pten-knockout mouse prostate cancer and TRAMP neuroendocrine carcinoma.

Sangyub Kim, Li Li, Jinhui Zhang, Cheng Jiang, Junxuan Lü.

   BACKGROUND: Metabolic reprograming is now a recognized hallmark of cancer. The prostate-specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene-conditional knockout (KO) mouse carcinogenesis model is highly desirable for studying prostate cancer biology and prevention due to its close resemblance of primary molecular defects and histopathological features of human prostate cancer. We have recently published macromolecular profiling of this model by proteomics and transcriptomics, denoting a preeminence of inflammation and myeloid suppressive immune cell features. Here, we performed metabolomic analyses of Pten-KO prostate versus wild type (WT) counterpart for discernable changes in the aqueous metabolites and contrasted to those in the TRAMP neuroendocrine carcinoma (NECa).
METHODS: Three matched pairs of tissue-specific conditional Pten-KO mouse prostate and WT prostate of litter/cage-mates at 20-22 weeks of age and three pairs of TRAMP NECa versus WT (28-31 weeks) were profiled for their global aqueous metabolite changes, using hydrophilic interaction liquid chromatography-tandem mass spectrometry.
RESULTS: The Pten-KO prostate increased purine nucleotide pools, cystathionine, and both reduced and oxidized glutathione (GSH, GSSG), and gluconate/glucuronate species in addition to cholesteryl sulfate and polyamine precursor ornithine. On the contrary, Pten-KO prostate contained diminished pools of glycolytic intermediates and phosphorylcholine derivatives, select amino acids, and their metabolites. Bioinformatic integration revealed a significant shunting of glucose away from glycolysis-citrate cycle and glycerol-lipid genesis to pentose phosphate cycle for NADPH/GSH/GSSG redox and pentose moieties for purine and pyrimidine nucleotides, and glycosylation/glucuronidation. Implicit arginine catabolism to ornithine was consistent with immunosuppression in Pten-KO model. While also increased in cystathionine-GSH/GSSG, purine, and pyrimidine nucleotide pools and glucuronidation at the expense of glycolysis-citrate cycle, the TRAMP NECa increased abundance of many amino acids, methyl donor S-adenosyl-methionine, and intermediates for phospholipids without increasing cholesteryl sulfate or ornithine.
CONCLUSIONS: The aqueous metabolomic patterns in Pten-KO prostate and TRAMP NECa shared similarities in the greater pools of cystathionine, GSH/GSSG redox pair, and nucleotides and shunting away from glycolysis-citrate cycle in both models. Remarkable metabolic distinctions between them included metabolisms of many amino acids (protein synthesis; arginine-ornithine/immune suppression) and cholesteryl sulfate and methylation donor for epigenetic regulations.

Keywords:  adenocarcinoma; metabolic biomarkers; neuroendocrine carcinoma; prostate cancer

DOI:  https://doi.org/10.1002/pros.24256