bims-polyam 2022-01-16 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2022–01–16
six papers selected by
Sebastian J. Hofer, University of Graz

Hypusinated EIF5A as a feasible drug target for Advanced Medicinal Therapies in the treatment of pathogenic parasites and therapy-resistant tumors.
Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells.
Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation.
Endogenous Polyamines and Ethylene Biosynthesis in Relation to Germination of Osmoprimed Brassica napus Seeds under Salt Stress.
Ornithine decarboxylase functions in both autophagy and apoptosis in response to ultraviolet B radiation injury.
Solid-Supported Amplification of Aggregation Emission: A Tetraphenylethylene-Cucurbit[6]uril@Hydroxyapatite-Based Supramolecular Sensing Assembly for the Detection of Spermine and Spermidine in Human Urine and Blood.

Amino Acids. 2022 Jan 09.

Hypusinated EIF5A as a feasible drug target for Advanced Medicinal Therapies in the treatment of pathogenic parasites and therapy-resistant tumors.

Annette Kaiser, Enzo Agostinelli.

  Cancer drug resistance, in particular in advanced stages such as metastasis and invasion is an emerging problem. Moreover, drug resistance of parasites causing poverty-related diseases is an enormous, global challenge for drug development in the future. To circumvent this problem of increasing resistance, the development of either novel small compounds or Advanced Medicinal Therapies have to be fostered. Polyamines have many fundamental cellular functions like DNA stabilization, protein translation, ion channel regulation, autophagy, apoptosis and mostly important, cell proliferation. Consequently, many antiproliferative drugs can be commonly administered either in cancer therapy or for the treatment of pathogenic parasites. Most important for cell proliferation is the triamine spermidine, since it is an important substrate in the biosynthesis of the posttranslational modification hypusine in eukaryotic initiation factor 5A (EIF5A). To date, no small compound has been identified that directly inhibits the precursor protein EIF5A. Moreover, only a few small molecule inhibitors of the two biosynthetic enzymes, i.e. deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) have been functionally characterized. However, it is evident that only some of the compounds have been applied in translational approaches, i.e. in murine models to analyze the function of this modified protein in cell proliferation. In recent years, the pharmaceutical industry shifted from small molecules beyond traditional pharmacology to new tools and methods to treat disorders involving signaling deregulation. In this review, we evaluate translational approaches on inhibition of EIF5A hypusination in pathogenic parasites and therapy-resistant tumors and discuss its feasibility for an application in Advanced Medicinal Therapies.

Keywords:  Advanced Medicinal Therapies; Cancer; Hypusine; Parasites

DOI:  https://doi.org/10.1007/s00726-021-03120-6
Cell Rep. 2022 Jan 11. pii: S2211-1247(21)01726-5. [Epub ahead of print]38(2): 110222

Polyamine import and accumulation causes immunomodulation in macrophages engulfing apoptotic cells.

Alexandra L McCubbrey, Shannon A McManus, Jazalle D McClendon, Stacey M Thomas, Hope B Chatwin, Julie A Reisz, Angelo D'Alessandro, Kara J Mould, Donna L Bratton, Peter M Henson, William J Janssen.

  Phagocytosis of apoptotic cells, termed efferocytosis, is critical for tissue homeostasis and drives anti-inflammatory programming in engulfing macrophages. Here, we assess metabolites in naive and inflammatory macrophages following engulfment of multiple cellular and non-cellular targets. Efferocytosis leads to increases in the arginine-derived polyamines, spermidine and spermine, in vitro and in vivo. Surprisingly, polyamine accumulation after efferocytosis does not arise from retention of apoptotic cell metabolites or de novo synthesis but from enhanced polyamine import that is dependent on Rac1, actin, and PI3 kinase. Blocking polyamine import prevents efferocytosis from suppressing macrophage interleukin (IL)-1β or IL-6. This identifies efferocytosis as a trigger for polyamine import and accumulation, and imported polyamines as mediators of efferocytosis-induced immune reprogramming.

Keywords:  apoptosis; arginine; efferocytosis; macrophage; metabolites; phagocytosis; polyamines

DOI:  https://doi.org/10.1016/j.celrep.2021.110222
Cells. 2022 Jan 04. pii: 164. [Epub ahead of print]11(1):

Overview of Polyamines as Nutrients for Human Healthy Long Life and Effect of Increased Polyamine Intake on DNA Methylation.

Kuniyasu Soda.

  Polyamines, spermidine and spermine, are synthesized in every living cell and are therefore contained in foods, especially in those that are thought to contribute to health and longevity. They have many physiological activities similar to those of antioxidant and anti-inflammatory substances such as polyphenols. These include antioxidant and anti-inflammatory properties, cell and gene protection, and autophagy activation. We have first reported that increased polyamine intake (spermidine much more so than spermine) over a long period increased blood spermine levels and inhibited aging-associated pathologies and pro-inflammatory status in humans and mice and extended life span of mice. However, it is unlikely that the life-extending effect of polyamines is exerted by the same bioactivity as polyphenols because most studies using polyphenols and antioxidants have failed to demonstrate their life-extending effects. Recent investigations revealed that aging-associated pathologies and lifespan are closely associated with DNA methylation, a regulatory mechanism of gene expression. There is a close relationship between polyamine metabolism and DNA methylation. We have shown that the changes in polyamine metabolism affect the concentrations of substances and enzyme activities involved in DNA methylation. I consider that the increased capability of regulation of DNA methylation by spermine is a key of healthy long life of humans.

Keywords:  DNA; DNA methyltransferases (DNMT); LFA-1 promoter (ITGAL); lymphocyte function-associated antigen 1 (LFA-1); methylation; polyamine; spermidine; spermine

DOI:  https://doi.org/10.3390/cells11010164
Int J Mol Sci. 2021 Dec 29. pii: 349. [Epub ahead of print]23(1):

Endogenous Polyamines and Ethylene Biosynthesis in Relation to Germination of Osmoprimed Brassica napus Seeds under Salt Stress.

Katarzyna Lechowska, Łukasz Wojtyla, Muriel Quinet, Szymon Kubala, Stanley Lutts, Małgorzata Garnczarska.

  Currently, seed priming is reported as an efficient and low-cost approach to increase crop yield, which could not only promote seed germination and improve plant growth state but also increase abiotic stress tolerance. Salinity represents one of the most significant abiotic stresses that alters multiple processes in plants. The accumulation of polyamines (PAs) in response to salt stress is one of the most remarkable plant metabolic responses. This paper examined the effect of osmopriming on endogenous polyamine metabolism at the germination and early seedling development of Brassica napus in relation to salinity tolerance. Free, conjugated and bound polyamines were analyzed, and changes in their accumulation were discussed with literature data. The most remarkable differences between the corresponding osmoprimed and unprimed seeds were visible in the free (spermine) and conjugated (putrescine, spermidine) fractions. The arginine decarboxylase pathway seems to be responsible for the accumulation of PAs in primed seeds. The obvious impact of seed priming on tyramine accumulation was also demonstrated. Moreover, the level of ethylene increased considerably in seedlings issued from primed seeds exposed to salt stress. It can be concluded that the polyamines are involved in creating the beneficial effect of osmopriming on germination and early growth of Brassica napus seedlings under saline conditions through moderate changes in their biosynthesis and accumulation.

Keywords:  germination; polyamines; priming; salinity; seeds

DOI:  https://doi.org/10.3390/ijms23010349
J Cell Physiol. 2022 Jan 12.

Ornithine decarboxylase functions in both autophagy and apoptosis in response to ultraviolet B radiation injury.

Yi-Liang Liu, I-Hsin Hsiao, Yen-Hung Lin, Chih-Li Lin, Ming-Shiou Jan, Hui-Chih Hung, Guang-Yaw Liu.

  We present a mechanism for how ornithine decarboxylase (ODC) regulates the crosstalk between autophagy and apoptosis. In cancer cells, low-intensity ultraviolet B (UVBL ) induces autophagy while high-intensity UVB (UVBH ) induces apoptosis. Overexpression of ODC decreases UVBL -induced autophagy by inhibiting Atg5-Atg12 conjugation and suppressing the expression of autophagy markers LC3, Atg7, Atg12, and BECN1 proteins. In contrast, when ODC-overexpressing cells are exposed to UVBH radiation, the levels of LC3-II, Atg5-Atg12 conjugate, BECN1, Atg7, and Atg12 increase, while the apoptosis marker cleaved-PARP proteins decrease, indicating that ODC overexpression induced UVBH -induced autophagy but inhibited UVBH -induced cellular apoptosis. Additionally, when exposed to UVBH radiation, silencing BECN1, Atg5, and Atg12 genes results in a decrease in the level of LC3-II proteins but an increase in the level of cleaved-PARP proteins, and apoptotic bodies were significantly increased while autophagosomes were significantly decreased. These findings imply that ODC inhibits apoptosis in cells via the autophagy pathway. The role of Atg12 in ODC-overexpressing cells exposed to UVBH radiation is investigated using site-directed mutagenesis. Our results indicate that the Atg12-D111S mutant has increased cell survival. The Atg12-ΔG186 mutant impairs autophagy and enhances apoptosis. We demonstrate that when ODC-overexpressing cells are silenced for the Atg12 protein, autophagy and apoptosis are strongly affected, and ODC-induced autophagy protects against UVBH -induced apoptosis via the Atg12 protein.

Keywords:  Atg12; Atg5; apoptosis; autophagy; ornithine decarboxylase; ultraviolet B

DOI:  https://doi.org/10.1002/jcp.30678
ACS Appl Bio Mater. 2021 Feb 15. 4(2): 1813-1822

Solid-Supported Amplification of Aggregation Emission: A Tetraphenylethylene-Cucurbit[6]uril@Hydroxyapatite-Based Supramolecular Sensing Assembly for the Detection of Spermine and Spermidine in Human Urine and Blood.

Viraj G Naik, Vikash Kumar, Achikanath C Bhasikuttan, Kavita Kadu, Sutapa Roy Ramanan, Akhil A Bhosle, Mainak Banerjee, Amrita Chatterjee.

  The development of sensitive and selective tools for the detection and quantification of biomarkers is important in the diagnosis and treatment of clinical diseases. Spermine (SP) and spermidine (SPD) act as biomarkers for early-stage diagnosis of cancer in humans as their increased levels in urine are indicative of abnormal biological processes associated with this fatal disease. In this study, we introduced a strategy for solid-supported amplification of the effective aggregation-induced-emission (AIE) effect of a water-soluble tetraphenylethylene (TPE)-based probe in developing a supramolecular sensing platform for the rapid, sensitive, and selective detection of SP and SPD in water. The nonemissive TPE derivative (TPEHP) forms a less emissive conjugate with hydroxyl cucurbit[6]uril (CB[6]OH) in water, which undergoes several-fold enhancement of effective emission upon electrostatic interaction with the solid surface of hydroxyapatite nanoparticles (HAp NPs), dispersed in the aqueous media. The corresponding three-component supramolecular assembly disrupts by the intrusion of SP and SPD in the CB[6] portal because of the stronger binding ability with CB[6], resulting in a turn-off fluorescence sensor for SP and SPD with enhanced sensitivity. The assembly-disassembly-based sensing mechanism was thoroughly demonstrated by carrying out isothermal titration calorimetry (ITC), spectroscopic, and microscopic experiments. The sensing system showed low limits of detection (LODs) of 1.4 × 10-8 and 3.6 × 10-8 M for SP and SPD, respectively, which are well below the required range for the early diagnosis of cancer. Besides, a good linear relationship was obtained for both SP and SPD. Nominal interference from various metal ions, anions, common chemicals, amino acids, and other biogenic amines makes this sensing platform suitable for the real-time, low-level measurement of spermine (and spermidine) in human urinary and blood samples.

Keywords:  amplification of aggregation emission; cucurbit[6]uril; hydroxyapatite nanoparticles; spermidine; spermine; supramolecular sensing assembly; water-soluble tetraphenylethylene

DOI:  https://doi.org/10.1021/acsabm.0c01527