bims-polyam 2024-04-28 papers

Issue of 2024–04–28
five papers selected by
Sebastian J. Hofer, University of Graz

Plants (Basel). 2024 Apr 15. pii: 1100. [Epub ahead of print]13(8):

Exogenous Spermidine Alleviated Low-Temperature Damage by Affecting Polyamine Metabolism and Antioxidant Levels in Apples.

Meiqi He, Jia Zhou, Deguo Lyu, Gongxun Xu, Sijun Qin.

Low-temperature stress significantly limits the growth, development, and geographical distribution of apple cultivation. Spermidine (Spd), a known plant growth regulator, plays a vital role in the plant's response to abiotic stress. Yet, the mechanisms by which exogenous Spd enhances cold resistance in apples remain poorly understood. Therefore, the present study analyzed the effects of exogenous Spd on antioxidant enzyme activity, polyamine metabolism, and related gene expression levels of 1-year-old apple branches under low-temperature stress. Treatment with exogenous Spd was found to stabilize branch tissue biofilms and significantly reduce the levels of reactive oxygen species by elevating proline content and boosting the activity of antioxidants such as superoxide dismutase. It also upregulated the activities of arginine decarboxylase, S-adenosylmethionine decarboxylase, and spermidine synthase and the expression levels of MdADC1, MdSAMDC1, and MdSPDS1 under low-temperature stress and led to the accumulation of large amounts of Spd and spermine. Moreover, compared with the 2 mmol·L-1 Spd treatment, the 1 mmol·L-1 Spd treatment increased the expression levels of cold-responsive genes MdCBF1/2/3, MdCOR47, and MdKIN1, significantly. The findings suggest that exogenous Spd can enhance cold resistance in apple branches significantly. This enhancement is achieved by modulating polyamine metabolism and improving antioxidant defense mechanisms, which could be exploited to improve apple cultivation under cold stress conditions.

Keywords: antioxidant enzymes; apple; cold resistance; polyamine metabolism; spermidine

DOI: https://doi.org/10.3390/plants13081100

Breast Cancer Res. 2024 Apr 23. 26(1): 70

AMD1 promotes breast cancer aggressiveness via a spermidine-eIF5A hypusination-TCF4 axis.

Ruocen Liao, Xingyu Chen, Qianhua Cao, Longchang Bai, Chenglong Ma, Zhijun Dai, Chenfang Dong.

BACKGROUND: Basal-like breast cancer (BLBC) is the most aggressive subtype of breast cancer due to its aggressive characteristics and lack of effective therapeutics. However, the mechanism underlying its aggressiveness remains largely unclear. S-adenosylmethionine decarboxylase proenzyme (AMD1) overexpression occurs specifically in BLBC. Here, we explored the potential molecular mechanisms and functions of AMD1 promoting the aggressiveness of BLBC.
METHODS: The potential effects of AMD1 on breast cancer cells were tested by western blotting, colony formation, cell proliferation assay, migration and invasion assay. The spermidine level was determined by high performance liquid chromatography. The methylation status of CpG sites within the AMD1 promoter was evaluated by bisulfite sequencing PCR. We elucidated the relationship between AMD1 and Sox10 by ChIP assays and quantitative real-time PCR. The effect of AMD1 expression on breast cancer cells was evaluated by in vitro and in vivo tumorigenesis model.
RESULTS: In this study, we showed that AMD1 expression was remarkably elevated in BLBC. AMD1 copy number amplification, hypomethylation of AMD1 promoter and transcription activity of Sox10 contributed to the overexpression of AMD1 in BLBC. AMD1 overexpression enhanced spermidine production, which enhanced eIF5A hypusination, activating translation of TCF4 with multiple conserved Pro-Pro motifs. Our studies showed that AMD1-mediated metabolic system of polyamine in BLBC cells promoted tumor cell proliferation and tumor growth. Clinically, elevated expression of AMD1 was correlated with high grade, metastasis and poor survival, indicating poor prognosis of breast cancer patients.
CONCLUSION: Our work reveals the critical association of AMD1-mediated spermidine-eIF5A hypusination-TCF4 axis with BLBC aggressiveness, indicating potential prognostic indicators and therapeutic targets for BLBC.

Keywords: AMD1; Basal-like breast cancer (BLBC); Hypusination; TCF4; eIF5A

DOI: https://doi.org/10.1186/s13058-024-01825-6

Animals (Basel). 2024 Apr 19. pii: 1228. [Epub ahead of print]14(8):

The Roles of Polyamines in Intestinal Development and Function in Piglets.

Bihui Tan, Dingfu Xiao, Jing Wang, Bi'e Tan.

The gastrointestinal tract plays crucial roles in the digestion and absorption of nutrients, as well as in maintenance of a functional barrier. The development and maturation of the intestine is important for piglets to maintain optimal growth and health. Polyamines are necessary for the proliferation and growth of enterocytes, which play a key role in differentiation, migration, remodeling and integrity of the intestinal mucosa after injury. This review elaborates the development of the structure and function of the intestine of piglets during embryonic, suckling and weaning periods, the utilization and metabolism of polyamines in the intestine, as well as the role of polyamines in intestinal development and mucosal repair. The nutritional intervention to improve intestinal development and functions by modulating polyamine metabolism in piglets is also put forward. These results may help to promote the adaption to weaning in pigs and provide useful information for the development and health of piglets.

Keywords: intestine development; nutritional intervention; piglets; polyamine metabolism

DOI: https://doi.org/10.3390/ani14081228

Front Cell Dev Biol. 2024 ;12 1331759

Characterization of polyamine metabolism predicts prognosis, immune profile, and therapeutic efficacy in lung adenocarcinoma patients.

Zhouhua Li, Yue Wu, Weichang Yang, Wenjun Wang, Jinbo Li, Xiaotian Huang, Yanqiang Yang, Xinyi Zhang, Xiaoqun Ye.

Background: Polyamine modification patterns in lung adenocarcinoma (LUAD) and their impact on prognosis, immune infiltration, and anti-tumor efficacy have not been systematically explored.
Methods: Patients from The Cancer Genome Atlas (TCGA) were classified into subtypes according to polyamine metabolism-related genes using the consensus clustering method, and the survival outcomes and immune profile were compared. Meanwhile, the geneCluster was constructed according to the differentially expressed genes (DEGs) of the subtypes. Subsequently, the polyamine metabolism-related score (PMRS) system was established using the least absolute shrinkage and selection operator (LASSO) multivariate regression analysis in the TCGA training cohort (n = 245), which can be applied to characterize the prognosis. To verify the predictive performance of the PMRS, the internal cohort (n = 245) and the external cohort (n = 244) were recruited. The relationship between the PMRS and immune infiltration and antitumor responses was investigated.
Results: Two distinct patterns (C1 and C2) were identified, in which the C1 subtype presented an adverse prognosis, high CD8+ T cell infiltration, tumor mutational burden (TMB), immune checkpoint, and low tumor immune dysfunction and exclusion (TIDE). Furthermore, two geneClusters were established, and similar findings were observed. The PMRS, including three genes (SMS, SMOX, and PSMC6), was then constructed to characterize the polyamine metabolic patterns, and the patients were divided into high- and low-PMRS groups. As confirmed by the validation cohort, the high-PMRS group possessed a poor prognosis. Moreover, external samples and immunohistochemistry confirmed that the three genes were highly expressed in tumor samples. Finally, immunotherapy and chemotherapy may be beneficial to the high-PMRS group based on the immunotherapy cohorts and low half-maximal inhibitory concentration (IC50) values.
Conclusion: We identified distinct polyamine modification patterns and established a PMRS to provide new insights into the mechanism of polyamine action and improve the current anti-tumor strategy of LUAD.

Keywords: immune; lung adenocarcinoma; molecular subtype; polyamine; prognosis

DOI: https://doi.org/10.3389/fcell.2024.1331759

Pharmacol Biochem Behav. 2024 Apr 20. pii: S0091-3057(24)00068-6. [Epub ahead of print] 173774

CaMKIIα mediates spermidine-induced memory enhancement in rats: A potential involvement of PKA/CREB pathway.

Mustafa Munir Mustafa Dahleh, Carlos Fernando Mello, Juliano Ferreira, Maribel Antonello Rubin, Marina Prigol, Gustavo Petri Guerra.

Memory consolidation is associated with the regulation of protein kinases, which impact synaptic functions and promote synaptogenesis. The administration of spermidine (SPD) has been shown to modulate major protein kinases associated with memory improvement, including the Ca2+-dependent protein kinase (PKC) and cAMP-dependent protein kinase (PKA), key players in the cAMP response element-binding protein (CREB) activation. Nevertheless, the initial mechanism underlying SPD-mediated memory consolidation remains unknown, as we hypothesize a potential involvement of the memory consolidation precursor, Ca2+/calmodulin-dependent protein kinase II-α (CaMKIIα), in this process. Based on this, our study aimed to investigate potential interactions among PKC, PKA, and CREB activation, mediated by CaMKIIα activation, in order to elucidate the SPD memory consolidation pathway. Our findings suggest that the post-training administration of the CaMKII inhibitor, KN-62 (0.25 nmol, intrahippocampal), prevented the memory enhancement induced by SPD (0.2 nmol, intrahippocampal) in the inhibitory avoidance task. Through western immunoblotting, we observed that phosphorylation of CaMKIIα in the hippocampus was facilitated 15 min after intrahippocampal SPD administration, resulting in the activation of PKA and CREB, 180 min after infusion, suggesting a possible sequential mechanism, since SPD with KN-62 infusion leads to a downregulation in CaMKIIα/PKA/CREB pathway. However, KN-62 does not alter the memory-facilitating effect of SPD on PKC, possibly demonstrating a parallel cascade in memory acquisition via PKA, without modulating CAMKIIα. These results suggest that memory enhancement induced by SPD administration involves crosstalk between CaMKIIα and PKA/CREB, with no PKC interaction.

Keywords: CREB; CaMKIIα; Memory; PKA; PKC; Spermidine

DOI: https://doi.org/10.1016/j.pbb.2024.173774