bims-polyam 2023-11-19 papers

Issue of 2023–11–19
four papers selected by
Sebastian J. Hofer, University of Graz

Br J Nutr. 2023 Nov 15. 1-28

Dietary polyamine intake and all-cause and cause-specific mortality in Japanese adults in the Takayama study.

Chisato Nagata, Keiko Wada, Michiyo Yamakawa, Yuma Nakashima, Masaaki Sugino, Tomoka Mori.

Epidemiological studies on the potential health effects of dietary polyamines are scarce.The present study aimed to estimate habitual intake of polyamines (putrescine, spermidine, and spermine) and examine whether spermidine intake is inversely associated with all-cause and cause-specific mortality in a population-based cohort study in Japan. The study included 13,355 men and 15,724 women aged 35 years and older. Diet was assessed via a validated food-frequency questionnaire at the baseline in 1992. The intake of polyamines was estimated mainly using databases of polyamine content in foods consumed among Japanese population. Sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality were estimated according to polyamine quartiles. During 16 years of follow-up, 2901 deaths in men and 2438 in women occurred. The intake of any polyamine was not significantly associated with all-cause or cause-specific mortality after controlling for covariates in men and women. There was a suggestive positive association between spermidine intake and cancer mortality in women: HRs for the highest vs. lowest quartile were 1.38 (95% CI 0.99, 1.93; P -trend =0.02). Our results did not provide support for the notion that dietary spermidine has beneficial effects on mortality. Further studies on dietary polyamines and longevity, as well as the morbidity of specific diseases, including cancer, are needed across populations with different dietary habits.

Keywords: Japanese; Mortality; Polyamines; Spermidine

DOI: https://doi.org/10.1017/S0007114523002465

Food Sci Nutr. 2023 Nov;11(11): 7242-7254

Wheat germ, a byproduct of the wheat milling industry, as a beneficial source of anti-aging polyamines: A quantitative comparison of various forms.

Maryam Mohajeri, Seyed Abdulmajid Ayatollahi, Farzad Kobarfard, Mohammad Goli, Maryam Khandan, Shaya Mokhtari, Mahmoud Khodadoost.

Polyamines have received a lot of attention since the 1990s because of their anti-aging, anti-chronic disease, and proliferative effects. Wheat germ was reported as one of the natural sources of high polyamine, especially spermidine. The current study used three types of wheat germ: group A was industrially separated germ from whole grain, group B was the commercially available germinated wheat germ, and group C was manually separated wheat germ from germinated grain. The polyamine content of putrescine, spermidine, and spermine has been determined using a simplified isocratic LC-MS/MS method. An optimized extraction procedure was performed on all seven samples for obtaining a polyamine-enriched extract. The three dominant carbomylated polyamines were identified by analyzing the extracted samples in order to determine their relative abundance. Wheat germ powders contain the highest amount of polyamines (220-337 μg/g) of which spermidine is one of the most important. Germinated wheat grains, on the other hand, contain the least amount of this polyamine. The commercially available separated wheat germs are suggested as a good nutrition source of these polyamines.

Keywords: HPLC‐MS/MS method; isobutyl chloroformate; polyamine extraction; wheat germ

DOI: https://doi.org/10.1002/fsn3.3650

Molecules. 2023 Nov 04. pii: 7429. [Epub ahead of print]28(21):

Polyamine-Derived Aminoaldehydes and Acrolein: Cytotoxicity, Reactivity and Analysis of the Induced Protein Modifications.

Marek Šebela, Michaela Rašková.

Polyamines participate in the processes of cell growth and development. The degradation branch of their metabolism involves amine oxidases. The oxidation of spermine, spermidine and putrescine releases hydrogen peroxide and the corresponding aminoaldehyde. Polyamine-derived aminoaldehydes have been found to be cytotoxic, and they represent the subject of this review. 3-aminopropanal disrupts the lysosomal membrane and triggers apoptosis or necrosis in the damaged cells. It is implicated in the pathogenesis of cerebral ischemia. Furthermore, 3-aminopropanal yields acrolein through the elimination of ammonia. This reactive aldehyde is also generated by the decomposition of aminoaldehydes produced in the reaction of serum amine oxidase with spermidine or spermine. In addition, acrolein is a common environmental pollutant. It causes covalent modifications of proteins, including carbonylation, the production of Michael-type adducts and cross-linking, and it has been associated with inflammation-related diseases. APAL and acrolein are detoxified by aldehyde dehydrogenases and other mechanisms. High-performance liquid chromatography, immunochemistry and mass spectrometry have been largely used to analyze the presence of polyamine-derived aminoaldehydes and protein modifications elicited by their effect. However, the main and still open challenge is to find clues for discovering clear linkages between aldehyde-induced modifications of specific proteins and the development of various diseases.

Keywords: 3-aminopropanal; Michael adduct; Schiff base; acrolein; aldehyde dehydrogenase; amine oxidase; aminoaldehyde; cytotoxicity; glutathione; protein modification

DOI: https://doi.org/10.3390/molecules28217429

Transl Cancer Res. 2023 Oct 31. 12(10): 2477-2492

A polyamine metabolism risk signature for predicting the prognosis and immune therapeutic response of kidney cancer.

Bo Li, Zheng Kong, Yang Liu, Bifeng Xu, Xun Liu, Shuai Li, Zhihong Zhang.

Background: Polyamine metabolism is critically involved in the proliferation and metastasis of tumor cells, including in kidney renal clear cell (KIRC) cancer. However, the molecular mechanisms underlying the effect of polyamines in KIRC cancer remain largely unknown.
Methods: The messenger RNA (mRNA) expression profile of KIRC was downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ArrayExpress database. Differential expression analysis was performed with the "limma" package in R. Univariate Cox regression and multivariable Cox regression were used to estimate correlation between variables and prognosis. Least absolute shrinkage and selection operator (LASSO) Cox regression analysis was employed to screen variables and construct a risk signature. A nomogram model was established using the risk signature and clinical variables. Receiver operating characteristic (ROC), calibration curve, and decision curve analysis (DCA) were used to assess the predicted accuracy and clinical benefit of the model.
Results: We identified nine differentially expressed polyamine metabolism-related genes (PMRGs) in TCGA-KIRC. Of these, six were closely associated with patients' outcomes. These six genes participated in different pathways and originated from different cell types within the tumor microenvironment (TME). Using the mRNA expression values of these genes, we constructed a 4-gene PMRG risk signature. Patients with high PMRG risk exhibited worse outcomes, and our analysis showed that the PMRG risk signature was an independent prognostic factor when clinical information was used as a covariate. We also found that multiple immune- or metabolism-related pathways were differentially enriched in high or low PMRG risk groups, suggesting that altering these pathways could lead to different clinical outcomes. Finally, in two external datasets, we found that the PMRG risk signature could predict the response of patients to immune therapy.
Conclusions: In summary, our study identified several potentially important PMRGs in KIRC and constructed a practical risk signature, which could serve as a foundation for further development of polyamine metabolism-based targeted therapies for KIRC.

Keywords: Kidney renal clear cell (KIRC); gene set variation analysis (GSVA); polyamine metabolism; prognosis

DOI: https://doi.org/10.21037/tcr-23-344