bims-polyam 2022-12-18 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2022–12–18
eight papers selected by
Sebastian J. Hofer, University of Graz

Silicon inhibits gummosis by promoting polyamine synthesis and repressing ethylene biosynthesis in peach.
Spermidine and 1,3-Diaminopropane Have Opposite Effects on the Final Stage of Cephalosporin C Biosynthesis in High-Yielding Acremonium chrysogenum Strain.
Ectomycorrhizal Fungi Modulate Pedunculate Oak's Heat Stress Responses through the Alternation of Polyamines, Phenolics, and Osmotica Content.
Development of a polyamine gene expression score for predicting prognosis and treatment response in clear cell renal cell carcinoma.
Insight into the Molecular Signature of Skeletal Muscle Characterizing Lifelong Football Players.
Two polyamines -responsive WRKY transcription factors from Anoectochilus roxburghii play opposite functions on flower development.
The Role of L-Arginine-NO System in Female Reproduction: A Narrative Review.
The pleiotropic roles of eIF5A in cellular life and its therapeutic potential in cancer.

Front Plant Sci. 2022 ;13 986688

Silicon inhibits gummosis by promoting polyamine synthesis and repressing ethylene biosynthesis in peach.

Huaifeng Gao, Xuelian Wu, Xiaoqing Yang, Maoxiang Sun, Jiahui Liang, Yuansong Xiao, Futian Peng.

  Silicon is a beneficial element for plant growth, as well as for improving plant resistance to multiple biotic and abiotic stresses. Gummosis is a common harmful disease in peach and is induced by many factors. However, the effect of silicon on gummosis of peach has not been determined yet. In this study, we reported that application of silicon significantly reduced gummosis by regulating biosynthesis of ethylene and polyamines in peach. Ethylene promoted the development of gummosis by inducing the expression of genes encoding cell wall degrading enzymes. While application of different types of polyamines, including spermidine and spermine, dramatically inhibited the occurrence of gummosis. Moreover, polyamines inhibited the ethylene biosynthesis by down-regulating expression of ethylene biosynthetic gene PpACS1 (1-aminocyclopropane -1-carboxylic acid synthase), as well as the enzymatic activity of ACS. We further found that application of silicon significantly restricted the development of gummosis in peach. Exogenous silicon dramatically inhibited expression of PpACS1 and the enzymatic activity of its product to reduce ethylene biosynthesis. Simultaneously, the activity of S-adenosylmethionine decarboxylase, a key enzyme in ployamines biosynthesis, was increased by 9.85% under silicon treatment, resulting in elevated accumulation of polyamines. Thus, our data proved that application of silicon restricted gummosis development by activating ployamines biosynthesis and inhibiting ethylene synthesis in peach.

Keywords:  ethylene; gummosis; peach; polyamine; silicon

DOI:  https://doi.org/10.3389/fpls.2022.986688
Int J Mol Sci. 2022 Nov 23. pii: 14625. [Epub ahead of print]23(23):

Spermidine and 1,3-Diaminopropane Have Opposite Effects on the Final Stage of Cephalosporin C Biosynthesis in High-Yielding Acremonium chrysogenum Strain.

Alexander A Zhgun, Mikhail A Eldarov.

  The addition of exogenous polyamines increases the production of antibiotic cephalosporin C (CPC) in Acremonium chrysogenum high-yielding (HY) strain during fermentation on a complex medium. However, the molecular basis of this phenomenon is still unknown. In the current study, we developed a special synthetic medium on which we revealed the opposite effect of polyamines. The addition of 1,3-diaminopropane resulted in an increase in the yield of CPC by 12-15%. However, the addition of spermidine resulted in a decrease in the yield of CPC by 14-15% and accumulation of its metabolic pathway precursor, deacetylcephalosporin C (DAC); the total amount of cephems (DAC and CPC) was the same as after the addition of DAP. This indicates that spermidine, but not 1,3-diaminopropane, affects the final stage of CPC biosynthesis, associated with the acetylation of its precursor. In both cases, upregulation of biosynthetic genes from beta-lactam BGCs occurred at the same level as compared to the control; expression of transport genes was at the control level. The opposite effect may be due to the fact that N1-acetylation is much more efficient during spermidine catabolism than for 1,3-diaminopropane. The addition of spermidine, but not 1,3-diaminopropane, depleted the pool of acetyl coenzyme A by more than two-fold compared to control, which could lead to the accumulation of DAC.

Keywords:  Acremonium chrysogenum; acetyl coenzyme A; biosynthesis of secondary metabolites; cephalosporin C; filamentous fungi; polyamines; spermidine

DOI:  https://doi.org/10.3390/ijms232314625
Plants (Basel). 2022 Dec 03. pii: 3360. [Epub ahead of print]11(23):

Ectomycorrhizal Fungi Modulate Pedunculate Oak's Heat Stress Responses through the Alternation of Polyamines, Phenolics, and Osmotica Content.

Marko Kebert, Saša Kostić, Eleonora Čapelja, Vanja Vuksanović, Srđan Stojnić, Anđelina Gavranović Markić, Milica Zlatković, Marina Milović, Vladislava Galović, Saša Orlović.

  The physiological and biochemical responses of pedunculate oaks (Quercus robur L.) to heat stress (HS) and mycorrhization (individually as well in combination) were estimated. One-year-old Q. robur seedlings were grown under controlled conditions in a pot experiment, inoculated with a commercial inoculum of ectomycorrhizal (ECM) fungi, and subjected to 72 h of heat stress (40 °C/30 °C day/night temperature, relative humidity 80%, photoperiod 16/8 h) in a climate chamber, and they were compared with seedlings that were grown at room temperature (RT). An in-depth analysis of certain well-known stress-related metrics such as proline, total phenolics, FRAP, ABTS, non-protein thiols, and lipid peroxidation revealed that mycorrhized oak seedlings were more resistant to heat stress (HS) than non-mycorrhized oaks. Additionally, levels of specific polyamines, total phenolics, flavonoids, and condensed tannins as well as osmotica (proline and glycine betaine) content were measured and compared between four treatments: plants inoculated with ectomycorrhizal fungi exposed to heat stress (ECM-HS) and those grown only at RT (ECM-RT) versus non-mycorrhized controls exposed to heat stress (NM-HS) and those grown only at room temperature (NM-RT). In ectomycorrhiza inoculated oak seedlings, heat stress led to not only a rise in proline, total phenols, FRAP, ABTS, non-protein thiols, and lipid peroxidation but a notable decrease in glycine betaine and flavonoids. Amounts of three main polyamines (putrescine, spermine, and spermidine) were quantified by using high-performance liquid chromatography coupled with fluorescent detection (HPLC/FLD) after derivatization with dansyl-chloride. Heat stress significantly increased putrescine levels in non-mycorrhized oak seedlings but had no effect on spermidine or spermine levels, whereas heat stress significantly increased all inspected polyamine levels in oak seedlings inoculated with ectomycorrhizal inoculum. Spermidine (SPD) and spermine (SPM) contents were significantly higher in ECM-inoculated plants during heat stress (approximately 940 and 630 nmol g-1 DW, respectively), whereas these compounds were present in smaller amounts in non-mycorrhized oak seedlings (between 510 and 550 nmol g-1 DW for Spd and between 350 and 450 nmol g-1 DW for Spm). These findings supported the priming and biofertilizer roles of ectomycorrhizal fungi in the mitigation of heat stress in pedunculate oaks by modification of polyamines, phenolics, and osmotica content.

Keywords:  Quercus robur; ectomycorrhizal fungi; heat stress; osmolytes; phenolics; polyamines; priming

DOI:  https://doi.org/10.3390/plants11233360
Front Immunol. 2022 ;13 1048204

Development of a polyamine gene expression score for predicting prognosis and treatment response in clear cell renal cell carcinoma.

Mei Chen, Zhenyu Nie, Denggao Huang, Yuanhui Gao, Hui Cao, Linlin Zheng, Shufang Zhang.

   Backgrounds: Polyamine metabolism (PM) is closely related to the tumor microenvironment (TME) and is involved in antitumor immunity. Clear cell renal cell carcinoma (ccRCC) not only has high immunogenicity but also has significant metabolic changes. However, the role of PM in the immune microenvironment of ccRCC remains unclear. This study aimed to reveal the prognostic value of PM-related genes (PMRGs) expression in ccRCC and their correlation with the TME.
Methods: The expression levels PMRGs in different cells were characterized with single-cell sequencing analysis. The PMRG expression pattern of 777 ccRCC patients was evaluated based on PMRGs. Unsupervised clustering analysis was used in identifying PMRG expression subtypes, and Lasso regression analysis was used in developing polyamine gene expression score (PGES), which was validated in external and internal data sets. The predictive value of PGES for immunotherapy was validated in the IMvigor210 cohort. Multiple algorithms were used in analyzing the correlation between PGES and immune cells. The sensitivity of PGES to chemotherapeutic drugs was analyzed with the "pRRophetic" package. We validated the genes that develop PGES in tissue samples. Finally, weighted gene co-expression network analysis was used in identifying the key PMRGs closely related to ccRCC, and cell function experiments were carried out.
Results: PMRGs were abundantly expressed on tumor cells, and PMRG expression was active in CD8+ T cells and fibroblasts. We identified three PMRG expression subtypes. Cancer and immune related pathways were active in PMRG expression cluster A, which had better prognosis. PGES exhibited excellent predictive value. The high-PGES group was characterized by high immune cell infiltration, high expression of T cell depletion markers, high tumor mutation burden and tumor immune dysfunction and exclusion, was insensitive to immunotherapy but sensitive to sunitinib, temsirolimus, and rapamycin, and had poor prognosis. Spermidine synthetase (SRM) has been identified as a key gene and is highly expressed in ccRCC at RNA and protein levels. SRM knockdown can inhibit ccRCC cell proliferation, migration, and invasion.
Conclusions: We revealed the biological characteristics of PMRG expression subtypes and developed PGES to accurately predict the prognosis of patients and response to immunotherapy.

Keywords:  clear cell renal cell carcinoma; immune escape; immunotherapy; multi-omics; polyamine metabolism; prognosis

DOI:  https://doi.org/10.3389/fimmu.2022.1048204
Int J Environ Res Public Health. 2022 Nov 28. pii: 15835. [Epub ahead of print]19(23):

Insight into the Molecular Signature of Skeletal Muscle Characterizing Lifelong Football Players.

Stefania Orrù, Esther Imperlini, Daniela Vitucci, Marianna Caterino, Annalisa Mandola, Morten Bredsgaard Randers, Jakob Friis Schmidt, Marie Hagman, Thomas Rostgaard Andersen, Peter Krustrup, Margherita Ruoppolo, Pasqualina Buono, Annamaria Mancini.

   BACKGROUND: Aging and sedentary behavior are independent risk factors for non-communicable diseases. An active lifestyle and structured physical activity are positively associated with a healthier quality of life in the elderly. Here, we explored the proteomic/metabolomic muscular signature induced by lifelong football training associated with successful aging.
METHODS: The study was performed on nine lifelong football players (67.3 ± 2.8 yrs) and nine aged-matched untrained subjects. We performed a proteomic/metabolomic approach on V. lateralis muscle biopsies; the obtained data were analyzed by means of different bioinformatic tools.
RESULTS: Our results indicated that lifelong football training is able to enhance the muscles' oxidative capacity in the elderly by promoting fatty acids as preferential energetic substrates and hence determining a healthier body composition and metabolic profile; furthermore, we showed that the total polyamine content is higher in lifelong football players' muscle, enforcing the involvement of polyamines in muscle growth and hypertrophy.
CONCLUSIONS: Lifelong football training, as a structured physical activity, significantly influences the expression of the proteins and metabolites involved in oxidative metabolism and muscle hypertrophy associated with successful aging.

Keywords:  lifelong football training; mitochondrial oxidative capacity; polyamines; successful aging

DOI:  https://doi.org/10.3390/ijerph192315835
Plant Sci. 2022 Dec 10. pii: S0168-9452(22)00391-0. [Epub ahead of print]327 111566

Two polyamines -responsive WRKY transcription factors from Anoectochilus roxburghii play opposite functions on flower development.

Bingcong Xing, Siqi Wan, Liyang Su, Muhammad Waheed Riaz, Lihong Li, Yulin Ju, Wangshu Zhang, Ying Zheng, Qingsong Shao.

  Anoectochilus roxburghii is a rare and precious plant with medicinal and healthcare functions. Embryo abortion caused the lack of resources. Polyamine promoted its flowering and stress resistance in our previous study. But the mechanism remains unclear. The WRKY transcription factor family has been linked to a variety of biological processes in plants. In this study, two WRKY TFs (ArWRKY5 and ArWRKY20) of A. roxburghii, which showed significant response to Spd treatment, were identified and functionally analyzed. Tissue specific expression analyzation showed both of them mostly present in the flower. And ArWRKY5 expressed highest in the flower bud stage (-1 Flowering), while ArWRKY20 showed the highest expression in earlier flower bud stage (-2 Flowering) and the expression gradually decreased with flowering. The transcriptional activation activity assay and subcellular localization revealed that ArWRKY5 and ArWRKY20 were located in the nucleus and ArWRKY20 showed transcriptional activity. The heterologous expression of ArWRKY5 in Arabidopsis thaliana showed earlier flowering, while overexpression of ArWRKY20 delayed flowering. But the OE-ArWRKY20 lines had a robust body shape and a very significant increase in the number of rosette leaves. Furthermore, stamens and seed development were positively regulated by these two ArWRKYs. These results indicated that ArWRKY5 and ArWRKY20 not only play opposite roles in the floral development, but also regulate the plant growth and seed development in A. thaliana. But their specific biological functions and mechanism in A. roxburghii need to be investigated further.

Keywords:  Anoectochilus roxburghii; Floral development; Polyamine; Regulation; WRKY transcription factor

DOI:  https://doi.org/10.1016/j.plantsci.2022.111566
Int J Mol Sci. 2022 Nov 28. pii: 14908. [Epub ahead of print]23(23):

The Role of L-Arginine-NO System in Female Reproduction: A Narrative Review.

Jozsef Bodis, Balint Farkas, Bernadett Nagy, Kalman Kovacs, Endre Sulyok.

  Accumulating evidence are available on the involvement of l-arginine-nitric oxide (NO) system in complex biological processes and numerous clinical conditions. Particular attention was made to reveal the association of l-arginine and methylarginines to outcome measures of women undergoing in vitro fertilization (IVF). This review attempts to summarize the expression and function of the essential elements of this system with particular reference to the different stages of female reproduction. A literature search was performed on the PubMed and Google Scholar systems. Publications were selected for evaluation according to the results presented in the Abstract. The regulatory role of NO during the period of folliculogenesis, oocyte maturation, fertilization, embryogenesis, implantation, placentation, pregnancy, and delivery was surveyed. The major aspects of cellular l-arginine uptake via cationic amino acid transporters (CATs), arginine catabolism by nitric oxide synthases (NOSs) to NO and l-citrulline and by arginase to ornithine, and polyamines are presented. The importance of NOS inhibition by methylated arginines and the redox-sensitive elements of the process of NO generation are also shown. The l-arginine-NO system plays a crucial role in all stages of female reproduction. Insufficiently low or excessively high rates of NO generation may have adverse influences on IVF outcome.

Keywords:  female reproduction; l-arginine; methylarginines; nitric oxide; oxidative stress

DOI:  https://doi.org/10.3390/ijms232314908
Biochem Soc Trans. 2022 Dec 16. 50(6): 1885-1895

The pleiotropic roles of eIF5A in cellular life and its therapeutic potential in cancer.

Aristeidis Panagiotis Sfakianos, Rebecca Mallory Raven, Anne Elizabeth Willis.

  Protein synthesis is dysregulated in the majority of cancers and this process therefore provides a good therapeutic target. Many novel anti-cancer agents are directed to target the initiation stage of translation, however, translation elongation also holds great potential as a therapeutic target. The elongation factor eIF5A that assists the formation of peptidyl bonds during the elongation process is of considerable interest in this regard. Overexpression of eIF5A has been linked with the development of a variety of cancers and inhibitors of the molecule have been proposed for anti-cancer clinical applications. eIF5A is the only protein in the cell that contains the post-translational modification hypusine. Hypusination is a two-step enzymatic process catalysed by the Deoxyhypusine Synthase (DHPS) and Deoxyhypusine Hydroxylase (DOHH). In addition, eIF5A can be acetylated by p300/CBP-associated factor (PCAF) which leads to translocation of the protein to the nucleus and its deactivation. In addition to the nucleus, eIF5A has been found in the mitochondria and the endoplasmic reticulum (ER) with eIF5A localisation related to function from regulation of mitochondrial activity and apoptosis to maintenance of ER integrity and control of the unfolded protein response (UPR). Given the pleiotropic functions of eIF5A and by extension the hypusination enzymes, this system is being considered as a target for a range of cancers including multiple myeloma, B-Cell lymphoma, and neuroblastoma. In this review, we explore the role of eIF5A and discuss the therapeutic strategies that are currently developing both in the pre- and the clinical stage.

Keywords:  DHPS; DOHH; cancer; eIF5A; hypusination; translation

DOI:  https://doi.org/10.1042/BST20221035