bims-polyam 2023-08-13 papers

Issue of 2023–08–13
four papers selected by
Sebastian J. Hofer, University of Graz

Theriogenology. 2023 Jul 22. pii: S0093-691X(23)00277-7. [Epub ahead of print]210 244-250

Correlation analysis of polyamine metabolism and reproductive hormone levels in goose ovarian follicles.

Dongmei Jiang, Chengweng Ji, Lijuan Kang, Weikang Ling, Zelong Wang, Xin Wang, Chunyang Niu, Yongni Guo, Qian Sun, Xiaoguang An, Bo Kang.

To investigate the relationship between polyamine metabolism and reproductive hormones in ovarian follicles of Sichuan white geese, follicle polyamine content and reproductive hormone levels and gene expressions related to polyamine metabolism, steroidogenesis and steroid hormone receptors were detected by HPLC, ELISA and RT-qPCR. The results showed that the overall trend of spermidine and spermine levels increased first and then decreased as increasing follicle size, with the highest level in F3 and F5 follicles (P < 0.05). Putrescine and 17β-estradiol (E2) levels in hierarchical follicles were significantly lower than those in prehierarchical follicles (P < 0.05). Progesterone (P4) first increased and then decreased, with the highest level in the F5 follicle (P < 0.05). The expression levels of estrogen receptor 1 (ER1) showed an overall increase as increasing follicle size (except in F3 follicles), while estrogen receptor 2 (ER2) in hierarchical follicles was significantly lower than that in the prehierarchical follicles (P < 0.05). In addition, the overall expression level of progesterone receptor (PR) decreased, with no significant differences among F1, F2 and F3 follicles (P > 0.05). Yolk putrescine contents were positively correlated with yolk E2 concentrations and PR expression levels (P < 0.05), A significant positive correlation of spermidine levels with yolk P4 concentrations and PR expressions was also observed, as well as the spermine levels with yolk P4 concentrations (P < 0.05). In summary, polyamines were involved in the regulation of follicular development in geese, and this regulation played a role in affecting steroidogenesis and the expression of genes related to hormone receptors.

Keywords: Follicular development; Goose; Hormone receptor; Polyamine; Steroid hormone

DOI: https://doi.org/10.1016/j.theriogenology.2023.07.026

Geroscience. 2023 Aug 07.

Association of spermidine blood levels with microstructure of sleep-implications from a population-based study.

Silke M Wortha, Juliane Schulz, Jevri Hanna, Claudia Schwarz, Beate Stubbe, Stefan Frenzel, Robin Bülow, Nele Friedrich, Matthias Nauck, Henry Völzke, Ralf Ewert, Antje Vogelgesang, Hans J Grabe, Julia Ladenbauer, Agnes Flöel.

Deteriorations in slow wave sleep (SWS) have been linked to brain aging and Alzheimer's disease (AD), possibly due to its key role in clearance of amyloid-beta and tau (Aß/tau), two pathogenic hallmarks of AD. Spermidine administration has been shown to improve sleep quality in animal models. So far, the association between spermidine levels in humans and parameters of SWS physiology are unknown but may be valuable for therapeutic strategies. Data from 216 participants (age range 50-81 years) of the population-based Study of Health in Pomerania TREND were included in our analysis. We investigated associations between spermidine plasma levels, key parameters of sleep macroarchitecture and microarchitecture that were previously associated with AD pathology, and brain health measured via a marker of structural brain atrophy (AD score). Higher spermidine levels were significantly associated with lower coupling between slow oscillations and spindle activity. No association was evident for SWS, slow oscillatory, and spindle activity throughout non-rapid eye movement sleep. Furthermore, elevated spermidine blood levels were significantly associated with a higher AD score, while sleep markers revealed no association with AD score. The association between higher spermidine levels and brain health was not mediated by coupling between slow oscillations and spindle activity. We report that higher spermidine blood levels are associated not only with deteriorated brain health but also with less advantageous markers of sleep quality in older adults. Future studies need to evaluate whether sleep, spermidine, and Aß/tau deposition are interrelated and whether sleep may play a mediating role.

Keywords: Alzheimer’s disease; Brain health; Sleep; Slow wave sleep; Spermidine

DOI: https://doi.org/10.1007/s11357-023-00886-3

bioRxiv. 2023 Jul 27. pii: 2023.07.25.550524. [Epub ahead of print]

Polyamine transport inhibition and cisplatin synergistically enhance tumor control through oxidative stress in murine head and neck cancer models.

Abdulkader Yassin-Kassab, Nathaniel Wang, Jackson Foley, Tracy Murray Stewart, Mark R Burns, Robert A Casero, R Alex Harbison, Umamaheswar Duvvuri.

Background: Surgery and/or platinum-based chemoradiation remain standard of care for patients with head and neck squamous cell carcinoma (HNSCC). While these therapies are effective in a subset of patients, a substantial proportion experience recurrence or treatment resistance. As cisplatin mediates cytotoxicity through oxidative stress while polyamines play a role in redox regulation, we posited that combining cisplatin with polyamine transport inhibitor, AMXT-1501, would increase oxidative stress and tumor cell death in HNSCC cells.
Methods: Cell proliferation was measured in syngeneic mouse HNSCC cell lines treated with cisplatin ± AMXT-1501. Synergy was determined by administering cisplatin and AMXT-1501 at a ratio of 1:10 to cancer cells in vitro . Cancer cells were transferred onto mouse flanks to test the efficacy of treatments in vivo . Reactive oxygen species (ROS) were measured. Cellular apoptosis was measured with flow cytometry using Annexin V/PI staining. High-performance liquid chromatography (HPLC) was used to quantify polyamines in cell lines. Cell viability and ROS were measured in the presence of exogenous cationic amino acids.
Results: The combination of cisplatin and AMXT-1501 synergize in vitro on HNSCC cell lines. In vivo combination treatment resulted in tumor growth inhibition greater than either treatment individually. The combination treatment increased ROS production and induced apoptotic cell death. HPLC revealed the synergistic mechanism was independent of intracellular polyamine levels. Supplementation of cationic amino acids partially rescued cancer cell viability and reduced ROS.
Conclusion: AMXT-1501 enhances the cytotoxic effects of cisplatin in vitro and in vivo in aggressive HNSCC cell lines through a polyamine-independent mechanism.

DOI: https://doi.org/10.1101/2023.07.25.550524

Curr Opin Struct Biol. 2023 Aug 03. pii: S0959-440X(23)00142-2. [Epub ahead of print]82 102668

Histone deacetylase 10: A polyamine deacetylase from the crystal structure to the first inhibitors.

Chiara Lambona, Clemens Zwergel, Rossella Fioravanti, Sergio Valente, Antonello Mai.

Polyamine deacetylase activity was discovered more than 40 years ago, but the responsible histone deacetylase 10 (HDAC10) was described only recently. HDAC10 is a class IIb HDAC, as is its closest relative, the α-tubulin deacetylase HDAC6. HDAC10 has attracted attention over the last 2 years due to its role in diseases, especially cancer. This review summarises chemical and structural biology approaches to the study of HDAC10. Light will be shed on recent advances in understanding the complex structural biology of HDAC10 and the discovery of the first highly selective HDAC10 inhibitors.

Keywords: Crystallography; HDAC10; HDAC10 inhibitors; HDAC10 substrates; Polyamine deacetylase

DOI: https://doi.org/10.1016/j.sbi.2023.102668