bims-polyam 2024-10-13 papers

Issue of 2024–10–13
five papers selected by
Sebastian J. Hofer, University of Graz

J Insect Sci. 2024 Sep 01. pii: 3. [Epub ahead of print]24(5):

Spermidine supplementation influence on protective enzymes of Apis mellifera (Hymenoptera: Apidae).

Tatjana V Čelić, Srđana Đorđievski, Elvira L Vukašinović, Ivan Pihler, Danijela Kojić, Jelena Purać.

Dietary supplementation has been proposed as a sustainable way to improve the health and resilience of honey bees (Apis mellifera, L.), as the decline in their numbers in recent decades has raised scientific, environmental, and economic concerns. Spermidine, a natural polyamine, has been shown to be a promising substance for honey bee supplementation, as its health-promoting effects have been demonstrated in numerous studies and in different organisms. As already shown, supplementation with spermidine at a certain concentration prolonged lifespan, reduced oxidative stress, and increased antioxidative capacity in honey bees. The aim of the present study was to investigate whether spermidine supplementation affects gene expression and/or enzyme activity of antioxidative and detoxification enzymes and immune response markers in honey bee workers. The different gene expression and enzyme activity patterns observed in abdominal and head tissues in response to spermidine supplementation suggest tissue-specific and concentration-dependent effects. In addition, the immune response markers suggest that spermidine has the ability to boost honey bee immunity. The observed changes make a valuable contribution to understanding the molecular mechanisms by which spermidine may exert its beneficial effects on the bee's health and lifespan. These results support the idea of the use of spermidine supplementation to promote bee health and resilience to environmental stressors, emphasizing that the dose must be carefully chosen to achieve a balance between the pro- and antioxidant effects of spermidine.

Keywords: antioxidative protection; immunity; nutrition; polyamine

DOI: https://doi.org/10.1093/jisesa/ieae098

Sci Rep. 2024 10 08. 14(1): 23465

Polyamine impact on physiology of early stages of reef-building corals-insights from rearing experiments and RNA-Seq analysis.

Kodai Gibu, Nanami Mizusawa, Mariko Iijima, Yoshikazu Ohno, Jun Yasumoto, Ko Yasumoto, Akira Iguchi.

Polyamines are involved in various functions related to the cellular-level responses. To assess effects of polyamines on marine organisms, rearing experiments and comprehensive gene expression analyses were conducted on Acropora digitifera and Acropora sp.1, representative reef-building corals along the west-central coast of Okinawa, Japan, to evaluate effects of putrescine. Concentrations of putrescine ≥ 1 mM dissolved tissues of juvenile polyps and increased mortality of planula larvae. RNA-Seq analysis of juvenile polyps exposed to putrescine at the stage before effects became visible revealed dynamic fluctuations in gene expression in the putrescine-treated samples, with increased expression of stress-responsive genes (e.g. NAD-dependent protein deacylase sirtuin-6) and the polyamine transporter Slc18b1-like protein. These results also suggest that putrescine affects expression of genes related to ribosomes and translation. This study provides important insights into roles of polyamines and future directions regarding physiological responses of corals.

DOI: https://doi.org/10.1038/s41598-024-72943-6

Cell Rep. 2024 Oct 09. pii: S2211-1247(24)01182-3. [Epub ahead of print]43(10): 114831

ERK1/2 interaction with DHPS regulates eIF5A deoxyhypusination independently of ERK kinase activity.

Andrew E Becker, Paweł Kochanowski, Pui-Kei Wu, Elżbieta Wątor, Wenjing Chen, Koushik Guchhait, Artur P Biela, Przemysław Grudnik, Jong-In Park.

This study explores a non-kinase effect of extracellular regulated kinases 1/2 (ERK1/2) on the interaction between deoxyhypusine synthase (DHPS) and its substrate, eukaryotic translation initiation factor 5A (eIF5A). We report that Raf/MEK/ERK activation decreases the DHPS-ERK1/2 interaction while increasing DHPS-eIF5A association in cells. We determined the cryoelectron microscopy (cryo-EM) structure of the DHPS-ERK2 complex at 3.5 Å to show that ERK2 hinders substrate entrance to the DHPS active site, subsequently inhibiting deoxyhypusination in vitro. In cells, impairing the ERK2 activation loop, but not the catalytic site, prolongs the DHPS-ERK2 interaction irrespective of Raf/MEK signaling. The ERK2 Ser-Pro-Ser motif, but not the common docking or F-site recognition sites, also regulates this complex. These data suggest that ERK1/2 dynamically regulate the DHPS-eIF5A interaction in response to Raf/MEK activity, regardless of its kinase function. In contrast, ERK1/2 kinase activity is necessary to regulate the expression of DHPS and eIF5A. These findings highlight an ERK1/2-mediated dual kinase-dependent and -independent regulation of deoxyhypusination.

Keywords: CP: Molecular biology; MAP kinase; Raf/MEK/ERK pathway; cryo-EM; cryogenic electron microscopy; deoxyhypusine synthase; eukaryotic translation initiation factor 5A; extracellular-signal-regulated kinase 1/2; hypusination; hypusine; non-kinase effect

DOI: https://doi.org/10.1016/j.celrep.2024.114831

ACS Infect Dis. 2024 Oct 09.

Spermidine Associated with Gut Microbiota Protects Against MRSA Bloodstream Infection by Promoting Macrophage M2 Polarization.

Qingqing Li, Ping Tian, Mingjuan Guo, Xiaoqiang Liu, Tingting Su, Mingyang Tang, Bao Meng, Liang Yu, Yi Yang, Yanyan Liu, Yasheng Li, Jiabin Li.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen that causes various diseases. Extensive researches highlight the significant role of gut microbiota and its metabolites, particularly spermidine, in infectious diseases. However, the immunomodulatory mechanisms of spermidine in MRSA-induced bloodstream infection remain unclear. Here, we confirmed the protective effects of spermidine in bloodstream infection in mice. Spermidine reduced the bacterial load and expression of inflammatory factors by shifting the macrophage phenotype to an anti-inflammatory phenotype, ultimately prolonging the survival of the infected mice. The protective effect against MRSA infection may rely on the elevated expression of protein tyrosine phosphatase nonreceptor 2 (PTPN2). Collectively, these findings confirm the immunoprotective effects of spermidine via binding to PTPN2 in MRSA bloodstream infection, providing new ideas for the treatment of related infectious diseases.

Keywords: PTPN2; bloodstream infection; gut microbiota; macrophages; methicillin-resistant Staphylococcus aureus; spermidine

DOI: https://doi.org/10.1021/acsinfecdis.3c00669

Pharmacol Res. 2024 Oct 09. pii: S1043-6618(24)00398-0. [Epub ahead of print] 107453

Novel deoxyhypusine synthase (DHPS) inhibitors target hypusination-induced vasculogenic mimicry (VM) against malignant melanoma.

Xi-He Zhao, Jian Ma, Jing-Si Guo, Kai-Li Liu, Yu-Xi Qin, Long-Tian Li, Ji-Fang Zhang, Yue-Ying Yang, Shi-Chen Zhang, Fan-Hao Meng, Lei Liu, Yue-Hui Yang, Xin-Yang Li.

Vasculogenic mimicry (VM) contributes factor to the poor prognosis of malignant melanoma. Developing deoxyhypusine synthase (DHPS) inhibitors against melanoma VM is clinically essential. In this study, we optimized and synthesized a series of compounds based on the candidate structure, and the hit compound 7k was identified through enzyme assay and cell viability inhibition screening. Both inside and outside the cell, 7k's ability to target DHPS and its high affinity were demonstrated. Molecular dynamics and point mutation indicated that mutations of K329 or V129 in DHPS abolish 7k's inhibitory activity. Using PCR arrays, solid-state antibody microarrays, and angiogenesis assays investigated 7k's impact on melanoma cells to reveal that DHPS regulates melanoma VM by promoting FGFR2 and c-KIT expression. Surprisingly, 7k was discovered to inhibit MC1R-mediated melanin synthesis in the zebrafish. Pharmacokinetic evaluations demonstrated 7k's favorable properties, and xenograft models evidenced its notable anti-melanoma efficacy, achieving a TGI of 73%. These results highlighted DHPS as key in melanoma VM formation and confirmed 7k's potential as a novel anti-melanoma agent.

Keywords: DHPS; Melanoma; Vasculogenic mimicry; eIF5A-Hypusine

DOI: https://doi.org/10.1016/j.phrs.2024.107453