bims-polyam Biomed News
on Polyamines
Issue of 2025–01–12
seven papers selected by
Sebastian J. Hofer, University of Graz
  1. Polyamine Metabolism and Functions: Key Roles in Cellular Health and Disease.
  2. The Association of Dietary Polyamines with Mortality and the Risk of Cardiovascular Disease: A Prospective Study in UK Biobank.
  3. Polyamine Adducts with AP Sites: Interaction with DNA Polymerases and AP Endonucleases.
  4. Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons.
  5. Administration of Spermidine and Eugenol Demonstrates Anti-Tumorigenic Efficacy on Metastatic SW620 and Primary Caco-2 Colorectal Cancer Spheroids.
  6. Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway.
  7. SMOX Inhibition Preserved Visual Acuity, Contrast Sensitivity, and Retinal Function and Reduced Neuro-Glial Injury in Mice During Prolonged Diabetes.
  1. Biomolecules. 2024 Dec 09. pii: 1570. [Epub ahead of print]14(12):
    Polyamine Metabolism and Functions: Key Roles in Cellular Health and Disease.
    Marianna Nicoletta Rossi, Manuela Cervelli.
      The polyamines putrescine, spermidine, and spermine are polycations ubiquitously present in cells, where they exert pleiotropic functions in cellular mechanisms like proliferation, protein synthesis (through the hypusination of the transcription factor EIF5a), redox balance, autophagy, and different forms of cell death [...].
    DOI:  https://doi.org/10.3390/biom14121570
  2. Nutrients. 2024 Dec 16. pii: 4335. [Epub ahead of print]16(24):
    The Association of Dietary Polyamines with Mortality and the Risk of Cardiovascular Disease: A Prospective Study in UK Biobank.
    Su Han, Mingxia Qian, Na Zhang, Rui Zhang, Min Liu, Jiangbo Wang, Furong Li, Liqiang Zheng, Zhaoqing Sun.
       BACKGROUND: Polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are essential for cellular physiology and various cellular processes. This study aimed to examine the associations of dietary polyamines intake and all-cause mortality and incident cardiovascular disease (CVD).
    METHODS: This prospective cohort study included 184,732 participants without CVD at baseline from the UK Biobank who had completed at least one dietary questionnaire. Diet was assessed using Oxford WebQ, a web-based 24 h recall questionnaire, with polyamines intakes estimated from previous studies. Cox proportional models with restricted cubic splines were employed to investigate nonlinear associations. The primary endpoint was all-cause mortality or incident CVD (including CVD death, coronary heart disease and stroke).
    RESULTS: During a median follow-up period of 11.5 years, 7348 (3.9%) participants died and 12,316 (6.5%) developed incident CVD. Polyamines intake showed nonlinear associations with all-cause mortality and incident CVD (P for nonlinear < 0.01). Compared to the lowest quintile group of dietary polyamines intake (≤17.4 mg/day), the quintile 2 to 5 groups demonstrated a reduced risk of all-cause mortality, with the lowest risk in quintile 2 group (>17.4-22.3 mg/day) (HR:0.82, 95% CI: 0.76-0.88). Similar results were observed for incident CVD, with the lowest risk in the quintile 4 group (>27.1-33.5 mg/day) (HR: 0.86, 95% CI: 0.82-0.92).
    CONCLUSIONS: We found that dietary polyamines intake was associated with a lower risk of all-cause mortality or incident CVD. Furthermore, our study identified an optimal range of dietary polyamines intake.
    Keywords:  cohort study; coronary heart disease; putrescine; spermidine; spermine; stroke
    DOI:  https://doi.org/10.3390/nu16244335
  3. Chem Res Toxicol. 2025 Jan 07.
    Polyamine Adducts with AP Sites: Interaction with DNA Polymerases and AP Endonucleases.
    Anna V Yudkina, Margarita M Amanova, Dmitry O Zharkov.
      Biological polyamines, such as spermine, spermidine, and putrescine, are abundant intracellular compounds mostly bound to nucleic acids. Due to their nucleophilic nature, polyamines easily react with apurinic/apyrimidinic (AP) sites, DNA lesions that are constantly formed in DNA by spontaneous base loss and as intermediates of base excision repair. A covalent intermediate is formed, promoting DNA strand cleavage at the AP site, and is later hydrolyzed regenerating the polyamine. Here we have investigated formation of AP site adducts with spermine and spermidine using sodium borohydride trapping technique and shown that they could persist in DNA for long enough to possibly interfere with cell's replication and transcription machinery. We demonstrate that both adducts placed internally into DNA are strongly blocking for DNA polymerases (Klenow fragment, phage RB69 polymerase, human polymerases β and κ) and direct dAMP incorporation in the rare bypass events. The internal AP site adducts with polyamines can be repaired, albeit rather slowly, by Escherichia coli endonuclease IV and yeast Apn1 but not by human AP endonuclease APE1 or E. coli exonuclease III, whereas the 3'-terminal adducts are substrates for the phosphodiesterase activities of all these AP endonucleases.
    DOI:  https://doi.org/10.1021/acs.chemrestox.4c00312
  4. Antioxidants (Basel). 2024 Dec 04. pii: 1482. [Epub ahead of print]13(12):
    Spermidine Enhances Mitochondrial Bioenergetics in Young and Aged Human-Induced Pluripotent Stem Cell-Derived Neurons.
    Leonora Szabo, Imane Lejri, Amandine Grimm, Anne Eckert.
      The accumulation of damaged mitochondria has long been considered a hallmark of the aging process. Among various factors, age-related mitochondrial alterations comprise bioenergetic impairments and disturbances in reactive oxygen species (ROS) control, thereby negatively affecting mitochondrial performance and ultimately accelerating aging. Previous studies have revealed that polyamine spermidine appears to exert health-protective and lifespan-promoting effects. Notably, recent findings have also described a spermidine-induced improvement in age-associated mitochondrial dysfunction, but the beneficial effects of spermidine on aged mitochondria have not been entirely examined yet. Here, we show that spermidine positively regulates several parameters related to mitochondrial bioenergetics and mitochondrial redox homeostasis in young and aged human-induced pluripotent stem cell-derived neurons. We report that spermidine treatment increases adenosine triphosphate production and mitochondrial membrane potential, which is accompanied by an attenuation in mitochondrial ROS levels in both age groups. Furthermore, we demonstrate a spermidine-mediated amelioration in mitochondrial respiration in both young and aged neurons. Overall, our findings suggest that nutritional spermidine supplementation might represent an attractive therapeutic approach to enhance mitochondrial function, consequently decelerating aging.
    Keywords:  aging; bioenergetics; induced pluripotent stem cell-derived neurons; mitochondria; oxidative stress; spermidine
    DOI:  https://doi.org/10.3390/antiox13121482
  5. Int J Mol Sci. 2024 Dec 13. pii: 13362. [Epub ahead of print]25(24):
    Administration of Spermidine and Eugenol Demonstrates Anti-Tumorigenic Efficacy on Metastatic SW620 and Primary Caco-2 Colorectal Cancer Spheroids.
    Silvia Dilloo, Anne Whittaker, Xinyue Chang, Eros D'Amen, Enzo Spisni, Silvana Hrelia, Cristina Angeloni, Marco Malaguti, Giovanni Dinelli, Francesca Truzzi.
      The anti-cancer potential of eugenol (EUG) is well recognized, whereas that of spermidine (SPD) is subject to dispute and requires further research. The anti-tumorigenic potential of wheat germ SPD (150 µM) and clove EUG (100 µM), alone, in combination as SPD+EUG (50 µM + 100 µM) and, as a supplement (SUPPL; 0.6 µM SPD + 50 µM EUG), was investigated on both metastatic SW620 and primary Caco-2 colorectal cancer (CRC) spheroids. Compared to untreated controls, all treatments significantly reduced the vitality and spheroid area, increased the necrotic area, and induced apoptosis on both cell-type spheroids after 96 h, with a reduced migration evident in 2D (two-dimensional) cultures after 48 h. The comparable anti-CRC effects of the SPD+EUG and the SUPPL reflected a wide-range dose efficacy of SPD and EUG. It is of note that SPD+EUG induced a synergistic effect on the increased caspase-3 expression and reduced the migration percentage in SW620. In more physiologically relevant intestinal equivalents (healthy enterocytes [NCM460], fibroblasts [L929], and monocytes [U937]) containing embedded SW620/Caco-2 spheroids, SPD+EUG administration significantly reduced the spheroid CEA marker and proliferation, whilst simultaneously increasing occludin, autophagy LC3-II expression, and monocyte differentiation, compared to the control models. Exogenous SPD, alone and in combination with EUG, displayed an anti-CRC potential on tumor growth and metastasis, and warrants further investigation.
    Keywords:  Caco-2 spheroids; SW620; anti-tumorigenic efficacy; apoptosis; co-culture intestinal equivalents; eugenol; migration; spermidine
    DOI:  https://doi.org/10.3390/ijms252413362
  6. Sci Rep. 2025 Jan 06. 15(1): 917
    Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway.
    Guannan Zhao, Xinxin Zhao, Ziping Liu, Baojin Wang, Peixin Dong, Hidemichi Watari, Lawrence M Pfeffer, Gabor Tigyi, Wenjing Zhang, Junming Yue.
      Deoxyhypusine synthase (DHPS) is an enzyme encoded by the DHPS gene, with high expression in various cancers, including ovarian cancer (OC). DHPS regulates the translation initiation factor EIF5A, and EIF5A2 knockout inhibits OC tumor growth and metastasis by blocking the epithelial-to-mesenchymal transition (EMT) and the TGFβ pathway. In this study, we show that DHPS is amplified in OC patients, and its elevated expression correlates with poor survival. Using lentiviral CRISPR/Cas9 vectors for DHPS knockout, we observed EMT inhibition in SKOV3 and OVCAR8 cells through suppressed hypusination and reduced EIF5A2 expression. Inhibition of DHPS activity with GC7 similarly blocked hypusination and EMT. Disrupting DHPS expression, either genetically or pharmacologically, inhibited primary tumor growth and metastasis in OC mouse models. These findings suggest that targeting DHPS and inhibiting hypusination could be promising strategies for OC treatment.
    Keywords:  DHPS; EIF5A; EMT; GC7; Hypusination; Metastasis; Orthotopic OC mouse models; Ovarian cancer; TGFβ
    DOI:  https://doi.org/10.1038/s41598-025-85466-5
  7. Cells. 2024 Dec 12. pii: 2049. [Epub ahead of print]13(24):
    SMOX Inhibition Preserved Visual Acuity, Contrast Sensitivity, and Retinal Function and Reduced Neuro-Glial Injury in Mice During Prolonged Diabetes.
    Moaddey Alfarhan, Fang Liu, Bayan R Matani, Payaningal R Somanath, S Priya Narayanan.
      Diabetic retinopathy, a major cause of vision loss, is characterized by neurovascular changes in the retina. The lack of effective treatments to preserve vision in diabetic patients remains a significant challenge. A previous study from our laboratory demonstrated that 12-week treatment with MDL 72527, a pharmacological inhibitor of spermine oxidase (SMOX, a critical regulator of polyamine metabolism), reduced neurodegeneration in diabetic mice. Utilizing the streptozotocin-induced diabetic mouse model and MDL 72527, the current study investigated the effectiveness of SMOX inhibition on the measures of vision impairment and neuro-glial injury following 24 weeks of diabetes. Reductions in visual acuity, contrast sensitivity, and inner retinal function in diabetic mice were improved by MDL 72527 treatment. Diabetes-induced changes in neuronal-specific class III tubulin (Tuj-1), synaptophysin, glutamine synthetase, and vimentin were attenuated in response to SMOX inhibition. In conclusion, our findings show that SMOX inhibition improved visual acuity, contrast sensitivity, and inner retinal function and mitigated diabetes-induced neuroglial damage during long-term diabetes. Targeting SMOX signaling may provide a potential strategy for reducing retinal neuronal damage and preserving vision in diabetes.
    Keywords:  MDL 72527; SMOX; contrast sensitivity; diabetic retinopathy; electroretinography; glial injury; neurodegeneration; visual acuity
    DOI:  https://doi.org/10.3390/cells13242049
This page is being maintained by Thomas Krichel. It was last updated on 2025‒01‒12 at 21:37.