bims-polyam 2024-10-27 papers

Issue of 2024–10–27
seven papers selected by
Sebastian J. Hofer, University of Graz

Physiol Rep. 2024 Oct;12(20): e70092

Effect of spermidine intake on skeletal muscle regeneration after chemical injury in male mice.

Tomohiro Iwata, Takanaga Shirai, Kazuki Uemichi, Riku Tanimura, Tohru Takemasa.

Skeletal muscle has a high regenerative ability and maintains homeostasis by rapidly regenerating from frequent damage caused by intense exercise or trauma. In sports, skeletal muscle damage occurs frequently due to intense exercise, so practical methods to promote skeletal muscle regeneration are required. Recent studies have shown that it may be possible to promote skeletal muscle regeneration through new pathways, such as promoting autophagy and improving mitochondrial function. Spermidine is a type of polyamine, and oral intake of spermidine promotes autophagy and improves mitochondrial function without inhibiting mTOR. Therefore, we evaluate the effects of spermidine intake on skeletal muscle regeneration after injury using a mouse model of cardiotoxin-induced muscle injury. Our results showed no significant change in skeletal muscle wet weight with spermidine intake at all time points. In addition, although spermidine intake significantly increased the mean fiber cross-sectional area 14 days after injury, these effects were not observed at other time points. In addition, we analyzed stem cells, autophagy, mTOR signaling, inflammation, and mitochondria, but no significant effects of spermidine intake were observed at almost all time points and protein expression levels. Therefore, spermidine intake does not affect skeletal muscle regeneration after chemical injury, and if there is any, it is very limited.

Keywords: autophagy; mTOR signaling; mitochondria; skeletal muscle regeneration; spermidine

DOI: https://doi.org/10.14814/phy2.70092

Z Naturforsch C J Biosci. 2024 Oct 24.

Spermidine protects cellular redox status and ionic homeostasis in D-galactose induced senescence and natural aging rat models.

Sandeep Singh, Avnish Kumar Verma, Geetika Garg, Abhishek Kumar Singh, Syed Ibrahim Rizvi.

Impaired redox homeostasis is an important hallmark of aging. Among various anti-aging interventions, caloric restriction mimetics (CRMs) are the most effective in promoting health and longevity. The potential role of spermidine (SPD) as a CRM in modulating oxidative stress and redox homeostasis during aging remains unclear. This study aimed to investigate the protective effect of SPD in D-galactose (D-gal) accelerated induced senescence model and naturally aged rats. Young male rats (4 months), D-gal induced (500 mg/kg b. w., subcutaneously) aging model and naturally aged (22 months) rats were supplemented with SPD (10 mg/kg b. w., orally) for 6 weeks. The results showed that SPD supplementation suppresses the age induced increase in reactive oxygen species, lipid peroxidation and protein oxidation. Additionally, it increases the level of antioxidants, plasma membrane redox system in erythrocytes and membrane. These results also indicate that membrane transporter activity is correlated with the susceptibility of the erythrocyte towards oxidative damage. We therefore present evidence that SPD improves redox status and membrane impairments in erythrocytes in experimental and naturally aging rat models, however, more research is required to recommend a potential therapeutic role for SPD as an anti-aging intervention strategy.

Keywords: aging; erythrocytes; membrane transporters; oxidative stress; spermidine

DOI: https://doi.org/10.1515/znc-2024-0181

Mol Reprod Dev. 2024 Oct;91(10): e70003

Combination of Exogenous Spermidine and Phosphocreatine Efficiently Improved the Quality and Antioxidant Capacity of Cryopreserved Boar Sperm and Reduced Apoptosis-Like Changes.

Jingchun Li, Hechuan Wang, Minghui Guo, Qing Guo, Yanbing Li.

The low resistance of boar sperm to cryopreservation dictates that addition antioxidants and energetic substances to the diluent to improve sperm quality is necessary. This study evaluated the effect of spermidine and phosphocreatine in combination on the quality, antioxidant capacity, and antiapoptotic-like changes capacity of cryopreserved boar sperm based on previous reports. The results showed that the combined application of spermidine and phosphocreatine significantly enhanced the motility, average path velocity, straight-line velocity, curvilinear velocity, beat cross frequency, acrosome integrity, plasma membrane integrity, mitochondrial activity, and DNA integrity compared with the control group (p < 0.05). In addition, the combined application of spermidine and phosphocreatine significantly enhanced the total antioxidant capacity, superoxide dismutase activity, glutathione peroxidase activity, and catalase activity while significantly decreasing malondialdehyde content and hydrogen peroxide content (p < 0.05). Western Blot analysis further showed that spermidine and phosphocreatine significantly decreased the expression of CASP3 and BAX and significantly enhanced the expression of BCL2 (p < 0.05); therefore, the combination of spermidine and phosphocreatine has potentially positive implications for improving the quality of cryopreserved boar sperm.

Keywords: antioxidant; apoptosis protein; boar sperm; cryopreservation; exogenous spermidine; phosphocreatine

DOI: https://doi.org/10.1002/mrd.70003

J Cancer Res Clin Oncol. 2024 Oct 23. 150(10): 473

Single-cell omics and machine learning integration to develop a polyamine metabolism-based risk score model in breast cancer patients.

Xiliang Zhang, Hanjie Guo, Xiaolong Li, Wei Tao, Xiaoqing Ma, Yuxing Zhang, Weidong Xiao.

BACKGROUND: Breast cancer remains the leading malignant neoplasm among women globally, posing significant challenges in terms of treatment and prognostic evaluation. The metabolic pathway of polyamines is crucial in breast cancer progression, with a strong association to the increased capabilities of tumor cells for proliferation, invasion, and metastasis.
METHODS: We used a multi-omics approach combining bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) to study polyamine metabolism. Data from The Cancer Genome Atlas, Gene Expression Omnibus, and Genotype-Tissue Expression identified 286 differentially expressed genes linked to polyamine pathways in breast cancer. These genes were analyzed using univariate COX and machine learning algorithms to develop a prognostic scoring algorithm. Single-cell RNA sequencing validated the model by examining gene expression heterogeneity at the cellular level.
RESULTS: Our single-cell analyses revealed distinct subpopulations with different expressions of genes related to polyamine metabolism, highlighting the heterogeneity of the tumor microenvironment. The SuperPC model (a constructed risk score) demonstrated high accuracy when predicting patient outcomes. The immune profiling and functional enrichment analyses revealed that the genes identified play a crucial role in cell cycle control and immune modulation. Single-cell validation confirmed that polyamine metabolism genes were present in specific cell clusters. This highlights their potential as therapeutic targets.
CONCLUSIONS: This study integrates single cell omics with machine-learning to develop a robust scoring model for breast cancer based on polyamine metabolic pathways. Our findings offer new insights into tumor heterogeneity, and a novel framework to personalize prognosis. Single-cell technologies are being used in this context to enhance our understanding of the complex molecular terrain of breast cancer and support more effective clinical management.

Keywords: Breast cancer; Machine learning; Polyamine metabolism; Risk scoring model

DOI: https://doi.org/10.1007/s00432-024-06001-z

Food Microbiol. 2025 Jan;pii: S0740-0020(24)00182-5. [Epub ahead of print]125 104644

Characterization of ornithine decarboxylase with histidine decarboxylase activity in natural histidine decarboxylase gene deletion Enterobacter hormaechei RH3.

Huijie Pei, Yilun Wang, Wei He, Yue Zhang, Lamei Yang, Jinhai Li, Yixuan Ma, Xinjie Hu, Shuhong Li, Jianlong Li, Kaidi Hu, Aiping Liu, Xiaolin Ao, Hui Teng, Ran Li, Qin Li, Likou Zou, Shuliang Liu, Yong Yang.

Histamine is predominantly produced in sausages via the decarboxylation of histidine by bacteria. Furthermore, histamine-producing bacteria usually possess the enzyme histidine decarboxylase (hdc). Enterobacter hormaechei RH3 isolated from sausages exhibited significant levels of histamine production despite the absence of hdc. In this study, we elucidated the previously unidentified mechanism underlying histamine production by RH3. We identified an enzyme, NehdX-772, exhibiting the hdc activity from the cell lysate supernatant of RH3, which was annotated as ornithine decarboxylase. The optimal activity of NehdX-772 was recorded at 35 °C and pH 6.0, and it could tolerate a salt concentration of 2.5% (w/v) NaCl. Moreover, artificial inoculation revealed that NehdX-772 was synthesized at significant levels in sausages, leading to an increase in histamine levels. The discovery of NehdX-772 explains the underlying mechanism of histamine production by RH3 and can be applied to decrease histamine production in sausages.

Keywords: Enterobacter hormaechei; Expression; Histamine; Inoculation; Ornithine decarboxylase

DOI: https://doi.org/10.1016/j.fm.2024.104644

Theriogenology. 2024 Oct 21. pii: S0093-691X(24)00431-X. [Epub ahead of print]231 133-143

Putrescine supplementation improves the developmental competence of in vitro produced bovine embryos.

Kubra Karakas Alkan, Fatma Satilmis, Gonca Sonmez, Yunus Emre Deniz, Muhammed Hudai Culha, Muhammed Furkan Ciftci, Omer Faruk Yesilkaya, Hasan Alkan.

The aim of this study was to investigate the effect of putrescine, anti-apoptotic, antioxidant, and a cell proliferation stimulant, on embryo development and quality by supplementing it to in vitro culture medium. In this study, oocytes were obtained from the ovaries of Holstein cattle. Following maturation and fertilization, the presumptive zygotes were randomly assigned to two groups. The first group (Putrescine, n = 435) was supplemented with putrescine at a concentration of 0.5 mM to in vitro culture. The second group (n = 407) was maintained under standard culture conditions without any supplementations to the medium. Following the determination of the developmental stages of the embryos, only those in the blastocyst stage were subjected to differential staining and the cell numbers of the embryos were determined. Moreover, the TUNEL assay was employed to ascertain the extent of cell death and the apoptotic index in the embryos. Additionally, the levels of ROS were determined in the embryos. Furthermore, gene expression analyses were conducted on blastocyst-stage embryos to ascertain the potential of putrescine supplementation in embryo development along specific pathways. Following in vitro culture, the blastocyst formation rate was 44.37 % in the putrescine group and 32.97 % in the control group (P < 0.05). The counts of ICM (60.60 ± 15.79 vs 50.73 ± 16.74), TE (117.70 ± 23.67 vs 94.0 ± 22.46), and TCC (178.30 ± 26.15 vs 144.73 ± 26.86) were found to be statistically higher in blastocysts developing after putrescine supplementation compared to the control group. Furthermore, the number of apoptotic cells (7.69 ± 2.17 vs 9.96 ± 3.99) and the apoptotic index (5.07 % vs 8.01 %) were found to be lower in the putrescine group in comparison to the control group. Nevertheless, it was established that the ROS level in the control group was approximately two-fold higher than in the putrescine group (P < 0.05). The findings also revealed that putrescine up-regulated the gene expression of SOD, GPX4, CAT, BCL2, NANOG and GATA3 while simultaneously down-regulating the BAX expression level. In conclusion, the supplementation of putrescine to the culture medium during in vitro bovine embryo production was found to contribute to the improvement of embryo quality and early embryonic development.

Keywords: Apoptosis; Embryo development; Gene expression; Putrescine; ROS

DOI: https://doi.org/10.1016/j.theriogenology.2024.10.017