bims-polyam Biomed News
on Polyamines
Issue of 2023‒10‒22
seven papers selected by
Sebastian J. Hofer, University of Graz
  1. Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging.
  2. Spermidine promotes fertility in aged female mice.
  3. Polyamines and hypusination are important for Clostridioides difficile toxin B (TcdB)-mediated activation of group 3 innate lymphocytes (ILC3s).
  4. Polyamine metabolism controls B-to-Z DNA transition to orchestrate DNA sensor cGAS activity.
  5. Alleviation role of exogenous cadaverine on cell cycle, endogenous polyamines amounts and biochemical enzyme changes in barley seedlings under drought stress.
  6. Improving postharvest life, quality and bioactive compounds of strawberry fruits using spermine and spermidine.
  7. Exogenous phytosulfokine α alleviates chilling injury of loquat fruit via regulating sugar, proline, polyamine and γ-aminobutyric acid metabolisms.
  1. Nat Aging. 2023 Oct 16.
    Polyamine metabolite spermidine rejuvenates oocyte quality by enhancing mitophagy during female reproductive aging.
    Yu Zhang, Jie Bai, Zhaokang Cui, Yu Li, Qian Gao, Yilong Miao, Bo Xiong.
      Advanced age is a primary risk factor for female infertility due to reduced ovarian reserve and declining oocyte quality. However, as an important contributing factor, the role of metabolic regulation during reproductive aging is poorly understood. Here, we applied untargeted metabolomics to identify spermidine as a critical metabolite in ovaries to protect oocytes against aging. In particular, we found that the spermidine level was reduced in ovaries of aged mice and that supplementation with spermidine promoted follicle development, oocyte maturation, early embryonic development and female fertility of aged mice. By microtranscriptomic analysis, we further discovered that spermidine-induced recovery of oocyte quality was mediated by enhancement of mitophagy activity and mitochondrial function in aged mice, and this mechanism of action was conserved in porcine oocytes under oxidative stress. Altogether, our findings suggest that spermidine supplementation could represent a therapeutic strategy to ameliorate oocyte quality and reproductive outcome in cis-gender women and other persons trying to conceive at an advanced age. Future work is needed to test whether this approach can be safely and effectively translated to humans.
    DOI:  https://doi.org/10.1038/s43587-023-00498-8
  2. Nat Aging. 2023 Oct 16.
    Spermidine promotes fertility in aged female mice.
    Andreas Zimmermann, Frank Madeo.
      
    DOI:  https://doi.org/10.1038/s43587-023-00495-x
  3. Infect Immun. 2023 Oct 20. e0023623
    Polyamines and hypusination are important for Clostridioides difficile toxin B (TcdB)-mediated activation of group 3 innate lymphocytes (ILC3s).
    Prakash Sah, Bailey A Knighten, Megan A Reidy, Lauren A Zenewicz.
      Clostridioides difficile is the most common cause of nosocomial gastrointestinal tract bacterial infections. We lack fully effective reliable treatments for this pathogen, and there is a critical need to better understand how C. difficile interacts with our immune system. Group 3 innate lymphocytes (ILC3s) are rare immune cells localized within mucosal tissues that protect against bacterial infections. Upon activation, ILC3s secrete high levels of the cytokine interleukin-22 (IL-22), which is a critical regulator of tissue responses during infection. C. difficile toxin B (TcdB), the major virulence factor, directly activates ILC3s, resulting in high IL-22 levels. We previously reported that polyamines are important in the activation of ILC3s by the innate cytokine interleukin-23 (IL-23) but did not identify a specific mechanism. In this study, we examine how a pathogen impacts a metabolic pathway important for immune cell function and hypothesized that polyamines are important in TcdB-mediated ILC3 activation. We show that TcdB upregulates the polyamine biosynthesis pathway, and the inhibition of the pathway decreases TcdB-mediated ILC3 activation. Two polyamines, putrescine and spermidine, are involved. Spermidine is the key polyamine in the hypusination of eukaryotic initiation factor 5A (eIF5A), and the inhibition of eIF5A reduced ILC3 activation. Thus, there is potential to leverage polyamines in ILC3s to promote activation of ILC3s during C. difficile infection and other bacterial infections where ILC3s serve a protective role.
    Keywords:  Clostridioides difficile; bacterial toxins; cytokines; innate lymphocytes; polyamines
    DOI:  https://doi.org/10.1128/iai.00236-23
  4. Immunity. 2023 Oct 08. pii: S1074-7613(23)00417-X. [Epub ahead of print]
    Polyamine metabolism controls B-to-Z DNA transition to orchestrate DNA sensor cGAS activity.
    Chunyuan Zhao, Yunjin Ma, Minghui Zhang, Xiaoyan Gao, Wenbo Liang, Ying Qin, Yue Fu, Mutian Jia, Hui Song, Chengjiang Gao, Wei Zhao.
      Cyclic guanosine monophosphate (GMP)-AMP (cGAMP) synthase (cGAS) is a universal double-stranded DNA (dsDNA) sensor that recognizes foreign and self-DNA in the cytoplasm and initiates innate immune responses and has been implicated in various infectious and non-infectious contexts. cGAS binds to the backbone of dsDNA and generates the second messenger, cGAMP, which activates the stimulator of interferon genes (STING). Here, we show that the endogenous polyamines spermine and spermidine attenuated cGAS activity and innate immune responses. Mechanistically, spermine and spermidine induced the transition of B-form DNA to Z-form DNA (Z-DNA), thereby decreasing its binding affinity with cGAS. Spermidine/spermine N1-acetyltransferase 1 (SAT1), the rate-limiting enzyme in polyamine catabolism that decreases the cellular concentrations of spermine and spermidine, enhanced cGAS activation by inhibiting cellular Z-DNA accumulation; SAT1 deficiency promoted herpes simplex virus 1 (HSV-1) replication in vivo. The results indicate that spermine and spermidine induce dsDNA to adopt the Z-form conformation and that SAT1-mediated polyamine metabolism orchestrates cGAS activity.
    Keywords:  B-DNA; Z-DNA; cGAS; innate immunity; polyamine metabolism; spermidine; spermine; type I IFNs
    DOI:  https://doi.org/10.1016/j.immuni.2023.09.012
  5. Sci Rep. 2023 Oct 15. 13(1): 17488
    Alleviation role of exogenous cadaverine on cell cycle, endogenous polyamines amounts and biochemical enzyme changes in barley seedlings under drought stress.
    Serkan Ozmen, Selma Tabur, Signem Oney-Birol.
      Cadaverine (Cad), which has an independent synthesis pathway compared to other polyamine (PA) types, contributes to the health of plants by regulating plant growth and development, abiotic stress tolerance and antioxidant defense mechanisms. In this work, experiments were carried out to understand the effects of exogenous Cad (10 µM) application under drought stress (%22 PEG 6000) and without stress on cell cycle, total protein content, endogenous PA levels, and biochemical enzyme activities in barley (Hordeum vulgare cv. Burakbey) considering the potential of Cad to stimulate the drought-related tolerance system. Cad application in a stress-free environment showed an effect almost like low-impact drought stress, causing changes in all parameters examined compared to samples grown in distilled water environment (Control). The results clearly show that Cad applied against the negative effects of drought stress on all parameters creates a drought resistance mechanism of the plant. Accordingly, Cad applied together with drought stress increased the density of cells in the cell cycle (G1-S and S-G2 phases) and the amount of endogenous (spermidine 10% and spermine 40%) PAs. In addition, while superoxide dismutase (SOD) (5%), (CAT) (55%) and ascorbate peroxidase (APX) (18%) enzyme levels increased, a stress response mechanism occurred due to the decrease in total protein content (20%) and malondialdehyde (MDA) (80%). As a result, exogenous application of 10 µM Cad showed that it reduced the negative effects of drought stress on endogenous PA amounts, cell division and biochemical activities in barley.
    DOI:  https://doi.org/10.1038/s41598-023-44795-z
  6. Braz J Biol. 2023 ;pii: S1519-69842023000100863. [Epub ahead of print]83 e273886
    Improving postharvest life, quality and bioactive compounds of strawberry fruits using spermine and spermidine.
    P Jalali, A R Zakerin, A H Aboutalebi-Jahromi, H Sadeghi.
      Small fruits such as strawberries, are a good source of natural antioxidants. In recent decades, many efforts have been made to increase the shelf life of strawberries and maintain its nutritional value in post-harvest conditions. In the present study, the effects of spermine (Spm) and spermidine (Spd) (0, 1.0 and 1.5 mM) on the post-harvest life and quality of strawberry fruits during the 3rd, 6th, and 12th days of storage, were investigated. Applications of Spm and Spd decreased the rate of weight loss, fruit decay, soluble solids content, fruit juice pH and taste index during the storage period in compared to the control. However, titratable acids and vitamin C contents, tissue stiffness, phenolic compounds and antioxidant activity increased in compared to the control. These growth regulators prevented the aging and loss of bioactive compounds of the fruit by increasing the antioxidant activity and preventing the destruction of the fruit tissue. Among the studied treatments, applications of 1.5 mM of Spm and Spd were the most effective treatments to enhance the storage life and quality characters of strawberry fruits.
    DOI:  https://doi.org/10.1590/1519-6984.273886
  7. Food Chem. 2023 Oct 13. pii: S0308-8146(23)02347-6. [Epub ahead of print]436 137729
    Exogenous phytosulfokine α alleviates chilling injury of loquat fruit via regulating sugar, proline, polyamine and γ-aminobutyric acid metabolisms.
    Yu Liu, Yuanyuan Hou, Binghan Yi, Yaqin Zhao, Yinqiu Bao, Zhengguo Wu, Yonghua Zheng, Peng Jin.
      Postharvest loquat fruit is susceptible to chilling injury (CI) under cold stress. In this study, the effects of phytosulfokine α (PSKα) on sugar, proline, polyamine and γ-aminobutyric acid (GABA) metabolisms in loquat fruit during cold storage were investigated. The results showed that PSKα treatment significantly increased PSKα content along with up-regulating EjPSK3 and EjPSK6 expressions, and inhibited the increases of internal browning index, electrolyte leakage and malondialdehyde (MDA) content of loquat fruit. Besides, PSKα treatment maintained higher reducing sugar, proline, polyamines, and GABA contents in loquat fruit via activating biosynthesis pathway and suppressing catabolism pathway. More importantly, the results of correlation analysis indicated that PSKα content displayed positive correlations with reducing sugar, proline, polyamines and GABA contents. These findings suggested that the improved chilling tolerance in PSKα-treated loquat fruit was due to enhancing reducing sugar, proline, polyamines, and GABA contents, which might be modulated by endogenous PSKα signaling.
    Keywords:  Chilling injury; Loquat fruit; Phytosulfokine α; Polyamine and GABA; Proline; Sugar
    DOI:  https://doi.org/10.1016/j.foodchem.2023.137729
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