bims-polyam 2021-03-07 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–03–07
nine papers selected by
Sebastian J. Hofer, University of Graz

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites.
Simultaneous Determination of Polyamines and Steroids in Human Serum from Breast Cancer Patients Using Liquid Chromatography-Tandem Mass Spectrometry.
Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro.
Update on the Roles of Polyamines in Fleshy Fruit Ripening, Senescence, and Quality.
Effects of Structural Isomers of Spermine on the Higher-Order Structure of DNA and Gene Expression.
A MYC-Driven Plasma Polyamine Signature for Early Detection of Ovarian Cancer.
Pre-implantation exogenous progesterone and pregnancy in sheep: I. polyamines, nutrient transport, and progestamedins.
Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential Anticancer Pd(II)-Agent.
Determination of Biogenic Amines in Different Parts of Lycium barbarum L. by HPLC with Precolumn Dansylation.

Aging (Albany NY). 2021 Mar 02. 13

Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites.

Claudia Grajeda-Iglesias, Sylvère Durand, Romain Daillère, Kristina Iribarren, Fabien Lemaitre, Lisa Derosa, Fanny Aprahamian, Noélie Bossut, Nitharsshini Nirmalathasan, Frank Madeo, Laurence Zitvogel, Guido Kroemer.

  The presence of Akkermansia muciniphila (Akk) in the human gut is associated with good health, leanness and fitness. Mouse experimentation has demonstrated positive effects for Akk, which counteracts aging, mediates antiobesity and antidiabetic effects, dampens inflammation and improves anticancer immunosurveillance. Clinical trials have confirmed antidiabetic effects for Akk. Here, we investigated the time-dependent effects of oral administration of Akk (which was live or pasteurized) and other bacteria to mice on the metabolome of the ileum, colon, liver and blood plasma. Metabolomics was performed by a combination of chromatographic and mass spectrometric methods, yielding a total of 1.637.227 measurements. Akk had major effects on metabolism, causing an increase in spermidine and other polyamines in the gut and in the liver. Pasteurized Akk (Akk-past) was more efficient than live Akk in elevating the intestinal concentrations of polyamines, short-chain fatty acids, 2-hydroxybutyrate, as well multiple bile acids, which also increased in the circulation. All these metabolites have previously been associated with human health, providing a biochemical basis for the beneficial effects of Akk.

Keywords:  Akkermansia muciniphila; fecal microbial transplantation; metabolomics; microbiota; polyamines

DOI:  https://doi.org/10.18632/aging.202739
Molecules. 2021 Feb 21. pii: 1153. [Epub ahead of print]26(4):

Simultaneous Determination of Polyamines and Steroids in Human Serum from Breast Cancer Patients Using Liquid Chromatography-Tandem Mass Spectrometry.

Yu Ra Lee, Ji Won Lee, Jongki Hong, Bong Chul Chung.

  A simultaneous quantitative profiling method for polyamines and steroids using liquid chromatography-tandem mass spectrometry was developed and validated. We applied this method to human serum samples to simultaneously evaluate polyamine and steroid levels. Chemical derivatization was performed using isobutyl chloroformate to increase the sensitivity of polyamines. The method was validated, and the matrix effects were in the range of 78.7-126.3% and recoveries were in the range of 87.8-123.6%. Moreover, the intra-day accuracy and precision were in the ranges of 86.5-116.2% and 0.6-21.8%, respectively, whereas the inter-day accuracy and precision were in the ranges of 82.0-119.3% and 0.3-20.2%, respectively. The linearity was greater than 0.99. The validated method was used to investigate the differences in polyamine and steroid levels between treated breast cancer patients and normal controls. In our results, N-acetyl putrescine, N-acetyl spermidine, cadaverine, 1,3-diaminopropane, and epitestosterone were significantly higher in the breast cancer patient group. Through receiver operating characteristic curve analysis, all metabolites that were significantly increased in patient groups with areas under the curve >0.8 were shown. This mass spectrometry-based quantitative profiling method, used for the investigation of breast cancer, is also applicable to androgen-dependent diseases and polyamine-related diseases.

Keywords:  breast cancer; liquid chromatography–tandem mass spectrometry; polyamine; serum; steroid

DOI:  https://doi.org/10.3390/molecules26041153
Viruses. 2021 Feb 16. pii: 310. [Epub ahead of print]13(2):

Polyamine Analog Diethylnorspermidine Restricts Coxsackievirus B3 and Is Overcome by 2A Protease Mutation In Vitro.

Bridget M Hulsebosch, Bryan C Mounce.

  Enteroviruses, including Coxsackievirus B3 (CVB3), are pervasive pathogens that cause significant disease, including cardiomyopathies. Unfortunately, no treatments or vaccines are available for infected individuals. We identified the host polyamine pathway as a potential drug target, as inhibiting polyamine biosynthesis significantly reduces enterovirus replication in vitro and in vivo. Here, we show that CVB3 is sensitive to polyamine depletion through the polyamine analog diethylnorspermidine (DENSpm), which enhances polyamine catabolism through induction of polyamine acetylation. We demonstrate that CVB3 acquires resistance to DENSpm via mutation of the 2A protease, which enhances proteolytic activity in the presence of DENSpm. Resistance to DENSpm occurred via mutation of a non-catalytic site mutation and results in decreased fitness. These data demonstrate that potential for targeting polyamine catabolism as an antiviral target as well as highlight a potential mechanism of resistance.

Keywords:  Coxsackievirus; enterovirus; polyamines; protease

DOI:  https://doi.org/10.3390/v13020310
Front Plant Sci. 2021 ;12 610313

Update on the Roles of Polyamines in Fleshy Fruit Ripening, Senescence, and Quality.

Fan Gao, Xurong Mei, Yuzhong Li, Jiaxuan Guo, Yuanyue Shen.

  Ripening of fleshy fruits involves complex physiological, biochemical, and molecular processes that coincide with various changes of the fruit, including texture, color, flavor, and aroma. The processes of ripening are controlled by ethylene in climacteric fruits and abscisic acid (ABA) in non-climacteric fruits. Increasing evidence is also uncovering an essential role for polyamines (PAs) in fruit ripening, especially in climacteric fruits. However, until recently breakthroughs have been made in understanding PA roles in the ripening of non-climacteric fruits. In this review, we compare the mechanisms underlying PA biosynthesis, metabolism, and action during ripening in climacteric and non-climacteric fruits at the physiological and molecular levels. The PA putrescine (Put) has a role opposite to that of spermidine/spermine (Spd/Spm) in cellular metabolism. Arginine decarboxylase (ADC) is crucial to Put biosynthesis in both climacteric and non-climacteric fruits. S-adenosylmethionine decarboxylase (SAMDC) catalyzes the conversion of Put to Spd/Spm, which marks a metabolic transition that is concomitant with the onset of fruit ripening, induced by Spd in climacteric fruits and by Spm in non-climacteric fruits. Once PA catabolism is activated by polyamine oxidase (PAO), fruit ripening and senescence are facilitated by the coordination of mechanisms that involve PAs, hydrogen peroxide (H2O2), ABA, ethylene, nitric oxide (NO), and calcium ions (Ca2+). Notably, a signal derived from PAO5-mediated PA metabolism has recently been identified in strawberry, a model system for non-climacteric fruits, providing a deeper understanding of the regulatory roles played by PAs in fleshy fruit ripening.

Keywords:  ABA; Ca2+; NO; ethylene; fruit ripening; polyamines; review

DOI:  https://doi.org/10.3389/fpls.2021.610313
Int J Mol Sci. 2021 Feb 26. pii: 2355. [Epub ahead of print]22(5):

Effects of Structural Isomers of Spermine on the Higher-Order Structure of DNA and Gene Expression.

Tomoki Kitagawa, Takashi Nishio, Yuko Yoshikawa, Naoki Umezawa, Tsunehiko Higuchi, Chwen-Yang Shew, Takahiro Kenmotsu, Kenichi Yoshikawa.

  Polyamines are involved in various biological functions, including cell proliferation, differentiation, gene regulation, etc. Recently, it was found that polyamines exhibit biphasic effects on gene expression: promotion and inhibition at low and high concentrations, respectively. Here, we compared the effects of three naturally occurring tetravalent polyamines, spermine (SPM), thermospermine (TSPM), and N4-aminopropylspermidine (BSPD). Based on the single DNA observation with fluorescence microscopy together with measurements by atomic force microscopy revealed that these polyamines induce shrinkage and then compaction of DNA molecules, at low and high concentrations, respectively. We also performed the observation to evaluate the effects of these polyamine isomers on the activity of gene expression by adapting a cell-free luciferase assay. Interestingly, the potency of their effects on the DNA conformation and also on the inhibition of gene expression activity indicates the highest for TSPM among spermine isomers. A numerical evaluation of the strength of the interaction of these polyamines with negatively charged double-strand DNA revealed that this ordering of the potency corresponds to the order of the strength of the attractive interaction between phosphate groups of DNA and positively charged amino groups of the polyamines.

Keywords:  bimodal effect of promotion and inhibition; gene expression; higher-order structure of DNA; polyamine

DOI:  https://doi.org/10.3390/ijms22052355
Cancers (Basel). 2021 Feb 22. pii: 913. [Epub ahead of print]13(4):

A MYC-Driven Plasma Polyamine Signature for Early Detection of Ovarian Cancer.

Johannes F Fahrmann, Ehsan Irajizad, Makoto Kobayashi, Jody Vykoukal, Jennifer B Dennison, Eunice Murage, Ranran Wu, James P Long, Kim-Anh Do, Joseph Celestino, Karen H Lu, Zhen Lu, Robert C Bast, Samir Hanash.

  MYC is an oncogenic driver in the pathogenesis of ovarian cancer. We previously demonstrated that MYC regulates polyamine metabolism in triple-negative breast cancer (TNBC) and that a plasma polyamine signature is associated with TNBC development and progression. We hypothesized that a similar plasma polyamine signature may associate with ovarian cancer (OvCa) development. Using mass spectrometry, four polyamines were quantified in plasma from 116 OvCa cases and 143 controls (71 healthy controls + 72 subjects with benign pelvic masses) (Test Set). Findings were validated in an independent plasma set from 61 early-stage OvCa cases and 71 healthy controls (Validation Set). Complementarity of polyamines with CA125 was also evaluated. Receiver operating characteristic area under the curve (AUC) of individual polyamines for distinguishing cases from healthy controls ranged from 0.74-0.88. A polyamine signature consisting of diacetylspermine + N-(3-acetamidopropyl)pyrrolidin-2-one in combination with CA125 developed in the Test Set yielded improvement in sensitivity at >99% specificity relative to CA125 alone (73.7% vs 62.2%; McNemar exact test 2-sided P: 0.019) in the validation set and captured 30.4% of cases that were missed with CA125 alone. Our findings reveal a MYC-driven plasma polyamine signature associated with OvCa that complemented CA125 in detecting early-stage ovarian cancer.

Keywords:  blood-based biomarkers; early detection; ovarian cancer; polyamines

DOI:  https://doi.org/10.3390/cancers13040913
J Anim Sci Biotechnol. 2021 Mar 05. 12(1): 39

Pre-implantation exogenous progesterone and pregnancy in sheep: I. polyamines, nutrient transport, and progestamedins.

Emily C Hoskins, Katherine M Halloran, Claire Stenhouse, Robyn M Moses, Kathrin A Dunlap, Michael C Satterfield, Heewon Seo, Gregory A Johnson, Guoyao Wu, Fuller W Bazer.

   BACKGROUND: Administration of exogenous progesterone (P4) to ewes during the pre-implantation period advances conceptus development and implantation. This study determined effects of exogenous P4 on transport of select nutrients and pathways that enhance conceptus development. Pregnant ewes (n = 38) were treated with either 25 mg P4 in 1 mL corn oil (P4, n = 18) or 1 mL corn oil alone (CO, n = 20) from day 1.5 through day 8 of pregnancy and hysterectomized on either day 9 or day 12 of pregnancy. Endometrial expression of genes encoding enzymes for synthesis of polyamines, transporters of glucose, arginine, and glycine, as well as progestamedins was determined by RT-qPCR.
RESULTS: On day 12 of pregnancy, conceptuses from P4-treated ewes had elongated while those from CO-treated ewes were spherical. The mRNA expression of AZIN2, an arginine decarboxylase, was lower in endometria of P4-treated than CO-treated ewes on day 9 of pregnancy. Expression of FGF10, a progestamedin, was greater in endometria of CO and P4-treated ewes on day 12 of gestation in addition to P4-treated ewes necropsied on day 9 of gestation. Treatment with P4 down-regulated endometrial expression of amino acid transporter SLC1A4 on day 12 of pregnancy.
CONCLUSIONS: Results indicated that administration of exogenous P4 during the pre-implantation period advanced the expression of FGF10, which may accelerate proliferation of trophectoderm cells, but also was correlated with decreased expression of glycine and serine transporters and polyamine synthesis enzyme AZIN2. Further research with increased sample sizes may determine how differential expression affects endometrial functions and potentially embryonic loss.

Keywords:  Amino acid; Endometrium; Gene expression; Polyamine; Progesterone

DOI:  https://doi.org/10.1186/s40104-021-00554-6
Metabolites. 2021 Feb 17. pii: 114. [Epub ahead of print]11(2):

Novel Insights into Mice Multi-Organ Metabolism upon Exposure to a Potential Anticancer Pd(II)-Agent.

Tatiana J Carneiro, Rita Araújo, Martin Vojtek, Salomé Gonçalves-Monteiro, Carmen Diniz, Ana L M Batista de Carvalho, M Paula M Marques, Ana M Gil.

  Pd(II)-compounds are presently regarded as promising anticancer drugs, as an alternative to Pt(II)-based drugs (e.g., cisplatin), which typically trigger severe side-effects and acquired resistance. Dinuclear Pd(II) complexes with biogenic polyamines such as spermine (Pd2Spm) have exhibited particularly beneficial cytotoxic properties, hence unveiling the importance of understanding their impact on organism metabolism. The present study reports the first nuclear magnetic resonance (NMR)-based metabolomics study to assess the in vivo impact of Pd2Spm on the metabolism of healthy mice, to identify metabolic markers with possible relation to biotoxicity/side-effects and their dynamics. The changes in the metabolic profiles of both aqueous and lipophilic extracts of mice kidney, liver, and breast tissues were evaluated, as a function of drug-exposure time, using cisplatin as a reference drug. A putative interpretation was advanced for the metabolic deviations specifically triggered by Pd2Spm, this compound generally inducing faster metabolic response and recovery to control levels for all organs tested, compared to cisplatin (except for kidney lipid metabolism). These results constitute encouraging preliminary metabolic data suggestive of potential lower negative effects of Pd2Spm administration.

Keywords:  NMR metabolomics; Pd2Spm; cisplatin; mice; palladium(II)-drugs; tissue extracts

DOI:  https://doi.org/10.3390/metabo11020114
Molecules. 2021 Feb 17. pii: 1046. [Epub ahead of print]26(4):

Determination of Biogenic Amines in Different Parts of Lycium barbarum L. by HPLC with Precolumn Dansylation.

Yun Ai, Yan Ni Sun, Li Liu, Fang Yuan Yao, Yan Zhang, Feng Yi Guo, Wen Jie Zhao, Jian Li Liu, Ning Zhang.

  The aim of this work was to characterize biogenic amines (BAs) in different parts of Lycium barbarum L. using HPLC with dansyl chloride derivatization, and jointly, to provide referential data for further exploration and utilization of Lycium barbarum L. The linear correlation coefficients for all BAs were above 0.9989. The limits of detection and quantification were 0.015-0.075 and 0.05-0.25 μg/mL, respectively. The relative standard deviations for the intra-day and inter-day precision were 0.66-2.69% and 0.91-4.38%. The described method has good repeatability and intermediate precision for the quantitative determination of BAs in different parts of Lycium barbarum L. Satisfactory recovery for all amines was obtained (79.3-110.3%). The result showed that there were four kinds of BAs. The highest putrescine content (20.9 ± 3.2 mg/kg) was found in the flower. The highest histamine content (102.7 ± 5.8 mg/kg) was detected in the bark, and the highest spermidine (13.3 ± 1.6 mg/kg) and spermine (23.7 ± 2.0 mg/kg) contents were detected in the young leaves. The high histamine (HIS) content in the bark may be one of the reasons why all of the parts of Lycium barbarum L., except the bark, are used for medicine or food in China. Meanwhile, the issue of the high concentration of HIS should be considered when exploiting or utilizing the bark of Lycium barbarum L.

Keywords:  HPLC; Lycium barbarum L.; biogenic amines; derivatization

DOI:  https://doi.org/10.3390/molecules26041046