bims-polyam 2024-09-01 papers

Issue of 2024‒09‒01
five papers selected by
Sebastian J. Hofer, University of Graz

Toxics. 2024 Aug 08. pii: 577. [Epub ahead of print]12(8):

The Accumulation of Abscisic Acid Increases the Innate Pool of Soluble Phenolics through Polyamine Metabolism in Rice Seedlings under Hexavalent Chromium Stress.

Yi Kang, Cheng-Zhi Li, Abid Ullah, Qing Zhang, Xiao-Zhang Yu.

Potential toxic element (PTE) pollution has emerged as a significant environmental and social concern in global agriculture. Chromium (Cr) occurs in different oxidation states naturally, among them Cr(VI), which is highly toxic. This study carried out biochemical and molecular tests to elucidate the accumulation of total soluble phenolics (TSPs) in rice plants exposed to Cr(VI) at 2.0, 8.0, and 16.0 mg Cr/L, emphasizing the interaction between polyamines (PAs) and abscisic acid (ABA). The results revealed significant Cr accumulation in different tissues of rice plants, which hindered their growth. Cr(VI) exposure increased the ABA concentration, with higher levels detected in the shoots than in the roots. The TSP concentration in rice tissues showed a positive relationship with the supplied concentrations of Cr(VI). The measured PAs, including spermine (Spm), putrescine (Put), and spermidine (Spd), exhibited varied responses to Cr(VI) stress, with only Spm concentration increasing with Cr(VI) concentrations. Real-time qRT-PCR showed PAs and ABA synthesis-associated genes such as OsADC1, OsAIH, OsCPA1, and OsCPA4 were significantly up-regulated in shoot of rice plants treated with Cr(VI). These genes are associated with the second pathway of Put synthesis, originating from Arg. Almost all genes activated in the Met pathway were significantly up-regulated as well. Moreover, the genes involved in the interconversion among the three species of PAs exhibited completely different responses to Cr(VI) exposure. Overall, the biochemical analysis and gene expression data indicate that the interaction between ABA and Spm is likely to enhance the TSP levels in rice plants subjected to Cr(VI) toxicity.

Keywords: abscisic acid; hexavalent chromium; rice; spermine; total soluble phenolics

DOI: https://doi.org/10.3390/toxics12080577

Nat Commun. 2024 Aug 28. 15(1): 7458

P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.

Xiangli Jiang, Ali Hyder Baig, Giuliana Palazzo, Rossella Del Pizzo, Toman Bortecen, Sven Groessl, Esther A Zaal, Cinthia Claudia Amaya Ramirez, Alexander Kowar, Daniela Aviles-Huerta, Celia R Berkers, Wilhelm Palm, Darjus Tschaharganeh, Jeroen Krijgsveld, Fabricio Loayza-Puch.

Cellular senescence is characterized by a permanent growth arrest and is associated with tissue aging and cancer. Senescent cells secrete a number of different cytokines referred to as the senescence-associated secretory phenotype (SASP), which impacts the surrounding tissue and immune response. Here, we find that senescent cells exhibit higher rates of protein synthesis compared to proliferating cells and identify eIF5A as a crucial regulator of this process. Polyamine metabolism and hypusination of eIF5A play a pivotal role in sustaining elevated levels of protein synthesis in senescent cells. Mechanistically, we identify a p53-dependent program in senescent cells that maintains hypusination levels of eIF5A. Finally, we demonstrate that functional eIF5A is required for synthesizing mitochondrial ribosomal proteins and monitoring the immune clearance of premalignant senescent cells in vivo. Our findings establish an important role of protein synthesis during cellular senescence and suggest a link between eIF5A, polyamine metabolism, and senescence immune surveillance.

DOI: https://doi.org/10.1038/s41467-024-51901-w

Biochim Biophys Acta Mol Cell Biol Lipids. 2024 Aug 22. pii: S1388-1981(24)00110-0. [Epub ahead of print] 159560

Spermidine mitigates ferroptosis in free fatty acid-induced AML-12 cells through the ATF4/SLC7A11/GCLM/GPX4 pathway.

Jia Zhang, Tao Zhang, Yihang Chen, Xiaojie Xuan, Yuqian Zhao, Gaofeng Lu.

Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of chronic liver disease worldwide. Spermidine (SPD), a naturally occurring polyamine, has shown potential in alleviating the accumulation of hepatic lipids and reducing NAFLD symptoms in overweight mice. Nonetheless, the specific mechanisms through which SPD exerts its effects remain largely unknown. This study seeks to explore the protective effects of SPD on NAFLD and to clarify the underlying mechanisms. An in vitro model of NAFLD was established by inducing steatosis in AML-12 cells through the use of free fatty acids (FFAs). Our experimental results demonstrate that SPD significantly reduces NAFLD development induced by FFAs. This reduction is primarily achieved through the inhibition of cellular ferroptosis, as evidenced by decreased levels of Fe2+, malondialdehyde (MDA), and reactive oxygen species (ROS). Additionally, SPD was found to enhance cellular activity and ameliorate mitochondrial dysfunction and oxidative stress caused by FFA exposure. Further mechanistic studies have revealed that SPD upregulates the expression of solute transporter family 7a member 11 (SLC7A11), glutamate-cysteine ligase modifier subunit (GCLM), and glutathione peroxidase (GPX4). This upregulation is mediated by the activation of activating transcription factor 4 (ATF4). Knockdown experiments of ATF4 confirmed that its inhibition reverses the upregulation of SLC7A11, GCLM, and GPX4, thereby negating the protective effects of SPD. In conclusion, our findings suggest that SPD mitigates NAFLD by modulating the ATF4/SLC7A11/GCLM/GPX4 signaling pathway, resulting in the suppression of ferroptosis and the improvement of cellular health. These insights provide a novel molecular mechanism and identify potential therapeutic targets for the treatment of NAFLD.

Keywords: Activating transcription factor 4; Ferroptosis; Non-alcoholic fatty liver disease; Oxidative stress; Spermidine

DOI: https://doi.org/10.1016/j.bbalip.2024.159560

J Pharm Biomed Anal. 2024 Aug 14. pii: S0731-7085(24)00458-8. [Epub ahead of print]251 116418

Simultaneous detection of 10 cancer-associated amino acids and polyamines by high-performance liquid chromatography-high resolution mass spectrometry in pleural effusion cells obtained from lung adenocarcinoma patients.

Tingting Wang, Yina Pan, Xiuhong Hu, Wenbo Ren, Li Li, Jing Huang.

The deregulation of amino acid and polyamine metabolism is a hallmark of malignancy that regulates cancer cell proliferation, angiogenesis, and invasion. A sensitive mass spectrometry method was developed to simultaneously quantify 10 cancer-associated metabolites in pleural effusion cells for the diagnosis of malignancy and to complement conventional pleural cytology. Analytes were detected by high-performance liquid chromatography-high resolution mass spectrometry (HPLC-HRMS) using C8-reversed-phase HPLC for separation and sequential window acquisition of all theoretical fragment ion spectra (SWATH) acquisition for obtaining high-resolution quantitative MS/MS chromatograms. This method was validated and applied to pleural effusion cells from patients with lung adenocarcinoma (LUAD, n = 48) and those from benign controls (n = 23). The range of the above metabolites was 2-200 ng/mL for proline, aspartate, ornithine, creatine, glutamine, glutamate, arginine, citrulline, and spermine and 10-1000 ng/mL for putrescine. The intra-assay and inter-assay coefficient of variation was below 13.70 % for all analytes. The joint detection of these metabolites in pleural effusion cells achieved a clinical sensitivity of 75.0 % and specificity of 95.7 % differentiating LUAD patients from benign controls. This assay enabled the detection of 10 cancer-associated metabolites in pleural effusion cells, and the increased concentration of these metabolites was correlated with the presence of LUAD.

Keywords: Cancer-associated metabolites; High-performance liquid chromatography-high resolution mass spectrometry; Lung adenocarcinoma; Pleural effusion

DOI: https://doi.org/10.1016/j.jpba.2024.116418

Int J Biol Macromol. 2024 Aug 26. pii: S0141-8130(24)05904-X. [Epub ahead of print]278(Pt 4): 135098

Synergistic anti-aging effect of Dendrobium officinale polysaccharide and spermidine: A metabolomics analysis focusing on the regulation of lipid, nucleotide and energy metabolism.

Hui Duan, Qun Yu, Yang Ni, Jinwei Li, Leilei Yu, Xiaowei Yan, Liuping Fan.

The importance of synergy has been underscored in recent medical research for augmenting the efficacy of therapeutic interventions, targeting multiple biological pathways simultaneously. Our prior research elucidated that Dendrobium officinale polysaccharide (DOP) has the potential to prolong the lifespan of Caenorhabditis elegans (C. elegans) via regulating gut microbiota. Concurrently, spermidine (Spd), as a mimicking caloric restriction, facilitates autophagy and exerts a pronounced anti-aging effect. To enhance the anti-aging capabilities of DOP, we conducted a comprehensive study examining the combined effects of DOP and Spd in C. elegans, incorporating metabolomics analysis to investigate the underlying mechanisms. A combination of 250 mg/L DOP and 29.0 mg/L Spd yielded the most favorable outcomes in lifespan extension, evidencing a synergistic effect with a combination index (CI) of 0.65. In oxidative and heat stress tolerance assays, the observed CIs were 0.50 and 0.33, respectively. Metabolomic analysis highlighted significant alterations in metabolites related to lipid, nucleotide and energy metabolism, notably regulating glycerol 3-phosphate, linoleoyl glycerol, docosapentaenoic acid and β-nicotinamide mononucleotide, nicotinamide adenine dinucleotide. The effects of DS on lipid metabolism were further validated using Oil Red O staining and triglyceride level in C. elegans. The results indicated that DS may primarily be via modulating lipid metabolism. To further confirm these findings, a high-fat diet-induced mouse model was employed. Consequently, it can be inferred that the synergistic anti-aging impact of DOP and Spd is likely mediated primarily through alterations in lipid metabolic processes.

Keywords: Dendrobium officinale polysaccharide; Spermidine; Synergistic anti-aging

DOI: https://doi.org/10.1016/j.ijbiomac.2024.135098