bims-polyam 2023-03-19 papers

Issue of 2023–03–19
six papers selected by
Sebastian J. Hofer, University of Graz

Sci Rep. 2023 Mar 15. 13(1): 4329

Spermidine dietary supplementation and polyamines level in reference to survival and lifespan of honey bees.

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

Honey bee health has been an important and ongoing topic in recent years. Honey bee is also an important model organism for aging studies. Polyamines, putrescine, spermidine and spermine, are ubiquitous polycations, involved in a wide range of cellular processes such as cell growth, gene regulation, immunity, and regulation of lifespan. Spermidine, named longevity elixir, has been most analysed in the context of aging. One of the several proposed mechanisms behind spermidine actions is antioxidative activity. In present study we showed that dietary spermidine supplementation: (a) improved survival, (b) increased the average lifespan, (c) influenced the content of endogenous polyamines by increasing the level of putrescine and spermidine and decreasing the level of spermine, (d) reduced oxidative stress (MDA level), (e) increased the antioxidant capacity of the organism (FRAP), (f) increased relative gene expression of five genes involved in polyamine metabolism, and (g) upregulated vitellogenin gene in honey bees. To our knowledge, this is the first study on honey bee polyamine levels in reference to their longevity. These results provide important information on possible strategies for improving honey bee health by introducing spermidine into their diet. Here, we offer spermidine concentrations that could be considered for that purpose.

DOI: https://doi.org/10.1038/s41598-023-31456-4

Sci Rep. 2023 Mar 15. 13(1): 4279

Polyamine-mediated mechanisms contribute to oxidative stress tolerance in Pseudomonas syringae.

Leandro Solmi, Franco R Rossi, Fernando M Romero, Marcel Bach-Pages, Gail M Preston, Oscar A Ruiz, Andrés Gárriz.

Bacterial phytopathogens living on the surface or within plant tissues may experience oxidative stress because of the triggered plant defense responses. Although it has been suggested that polyamines can defend bacteria from this stress, the mechanism behind this action is not entirely understood. In this study, we investigated the effects of oxidative stress on the polyamine homeostasis of the plant pathogen Pseudomonas syringae and the functions of these compounds in bacterial stress tolerance. We demonstrated that bacteria respond to H2O2 by increasing the external levels of the polyamine putrescine while maintaining the inner concentrations of this compound as well as the analogue amine spermidine. In line with this, adding exogenous putrescine to media increased bacterial tolerance to H2O2. Deletion of arginine decarboxylase (speA) and ornithine decarboxylate (speC), prevented the synthesis of putrescine and augmented susceptibility to H2O2, whereas targeting spermidine synthesis alone through deletion of spermidine synthase (speE) increased the level of extracellular putrescine and enhanced H2O2 tolerance. Further research demonstrated that the increased tolerance of the ΔspeE mutant correlated with higher expression of H2O2-degrading catalases and enhanced outer cell membrane stability. Thus, this work demonstrates previously unrecognized connections between bacterial defense mechanisms against oxidative stress and the polyamine metabolism.

DOI: https://doi.org/10.1038/s41598-023-31239-x

J Gen Physiol. 2023 05 01. pii: e202213273. [Epub ahead of print]155(5):

Blockade of TRPV channels by intracellular spermine.

Grigory Maksaev, Peng Yuan, Colin G Nichols.

The Vanilloid thermoTRP (TRPV1-4) subfamily of TRP channels are involved in thermoregulation, osmoregulation, itch and pain perception, (neuro)inflammation and immune response, and tight control of channel activity is required for perception of noxious stimuli and pain. Here we report voltage-dependent modulation of each of human TRPV1, 3, and 4 by the endogenous intracellular polyamine spermine. As in inward rectifier K channels, currents are blocked in a strongly voltage-dependent manner, but, as in cyclic nucleotide-gated channels, the blockade is substantially reduced at more positive voltages, with maximal blockade in the vicinity of zero voltage. A kinetic model of inhibition suggests two independent spermine binding sites with different affinities as well as different degrees of polyamine permeability in TRPV1, 3, and 4. Given that block and relief occur over the physiological voltage range of action potentials, voltage-dependent polyamine block may be a potent modulator of TRPV-dependent excitability in multiple cell types.

DOI: https://doi.org/10.1085/jgp.202213273

Biotechnol Biofuels Bioprod. 2023 Mar 14. 16(1): 46

Simultaneous expression of an endogenous spermidine synthase and a butanol dehydrogenase from Thermoanaerobacter pseudethanolicus in Clostridium thermocellum results in increased resistance to acetic acid and furans, increased ethanol production and an increase in thermotolerance.

Sun-Ki Kim, Yannick J Bomble, Janet Westpheling.

BACKGROUND: Sensitivity to inhibitors derived from the pretreatment of plant biomass is a barrier to the consolidated bioprocessing of these complex substrates to fuels and chemicals by microbes. Spermidine is a low molecular weight aliphatic nitrogen compound ubiquitous in microorganisms, plants, and animals and is often associated with tolerance to stress. We recently showed that overexpression of the endogenous spermidine synthase enhanced tolerance of the Gram-positive bacterium, Clostridium thermocellum to the furan derivatives furfural and HMF.
RESULTS: Here we show that co-expression with an NADPH-dependent heat-stable butanol dehydrogenase from Thermoanaerobacter pseudethanolicus further enhanced tolerance to furans and acetic acid and most strikingly resulted in an increase in thermotolerance at 65 °C.
CONCLUSIONS: Tolerance to fermentation inhibitors will facilitate the use of plant biomass substrates by thermophiles in general and this organism in particular. The ability to grow C. thermocellum at 65 °C has profound implications for metabolic engineering.

Keywords: Biofuels; Butanol dehydrogenase; Clostridium thermocellum; Inhibitor tolerance; Spermidine

DOI: https://doi.org/10.1186/s13068-023-02291-6

Cell Commun Signal. 2023 Mar 13. 21(1): 54

Eukaryotic Initiation Factor 5A2 localizes to actively translating ribosomes to promote cancer cell protrusions and invasive capacity.

Arantxa Martínez-Férriz, Carolina Gandía, José Miguel Pardo-Sánchez, Alihamze Fathinajafabadi, Alejandro Ferrando, Rosa Farràs.

BACKGROUND: Eukaryotic Initiation Factor 5A (eIF-5A), an essential translation factor, is post-translationally activated by the polyamine spermidine. Two human genes encode eIF-5A, being eIF5-A1 constitutively expressed whereas eIF5-A2 is frequently found overexpressed in human tumours. The contribution of both isoforms with regard to cellular proliferation and invasion in non-small cell lung cancer remains to be characterized.
METHODS: We have evaluated the use of eIF-5A2 gene as prognosis marker in lung adenocarcinoma (LUAD) patients and validated in immunocompromised mice. We have used cell migration and cell proliferation assays in LUAD lines after silencing each eIF-5A isoform to monitor their contribution to both phenotypes. Cytoskeleton alterations were analysed in the same cells by rhodamine-phalloidin staining and fluorescence microscopy. Polysome profiles were used to monitor the effect of eIF-5A2 overexpression on translation. Western blotting was used to study the levels of eIF-5A2 client proteins involved in migration upon TGFB1 stimulation. Finally, we have co-localized eIF-5A2 with puromycin to visualize the subcellular pattern of actively translating ribosomes.
RESULTS: We describe the differential functions of both eIF-5A isoforms, to show that eIF5-A2 properties on cell proliferation and migration are coincident with its features as a poor prognosis marker. Silencing of eIF-5A2 leads to more dramatic consequences of cellular proliferation and migration compared to eIF-5A1. Overexpression of eIF-5A2 leads to enhanced global translation. We also show that TGFβ signalling enhances the expression and activity of eIF-5A2 which promotes the translation of polyproline rich proteins involved in cytoskeleton and motility features as it is the case of Fibronectin, SNAI1, Ezrin and FHOD1. With the use of puromycin labelling we have co-localized active ribosomes with eIF-5A2 not only in cytosol but also in areas of cellular protrusion. We have shown the bulk invasive capacity of cells overexpressing eIF-5A2 in mice.
CONCLUSIONS: We propose the existence of a coordinated temporal and positional interaction between TFGB and eIF-5A2 pathways to promote cell migration in NSCLC. We suggest that the co-localization of actively translating ribosomes with hypusinated eIF-5A2 facilitates the translation of key proteins not only in the cytosol but also in areas of cellular protrusion. Video Abstract.

Keywords: Cell migration; Cytoskeleton organization; Eukaryotic translation initiation factor 5A2; Lung adenocarcinoma; TGFB1 signaling; Translating ribosomes

DOI: https://doi.org/10.1186/s12964-023-01076-6

Cancer Lett. 2023 Mar 10. pii: S0304-3835(23)00075-7. [Epub ahead of print] 216124

MYC-driven U2SURP regulates alternative splicing of SAT1 to promote triple-negative breast cancer progression.

Ling Deng, Li Liao, Yin-Ling Zhang, Shu-Yuan Hu, Shao-Ying Yang, Xiao-Yan Ma, Min-Ying Huang, Fang-Lin Zhang, Da-Qiang Li.

Triple-negative breast cancer (TNBC), although highly lethal, lacks validated therapeutic targets. Here, we report that U2 snRNP-associated SURP motif-containing protein (U2SURP), a poorly defined member of the serine/arginine rich protein family, was significantly upregulated in TNBC tumors, and its high expression was associated with poor prognosis. MYC, a frequently amplified oncogene in TNBC tumors, enhanced U2SURP translation through an eIF3D (eukaryotic translation initiation factor 3 subunit D)-dependent mechanism, resulting in accumulation of U2SURP in TNBC tissues. Functional assays revealed that U2SURP played an important role in facilitating tumorigenesis and metastasis of TNBC both in vitro and in vivo. Intriguingly, U2SURP had no significant effects on proliferation, migratory and invasive potential of normal mammary epithelial cells. Furthermore, we found that U2SURP promoted alternative splicing of spermidine/spermine N1-acetyltransferase 1 (SAT1) pre-mRNA by removal of intron 3, increasing the stability of SAT1 mRNA and subsequent protein expression levels. Importantly, spliced SAT1 promoted the oncogenic properties of TNBC cells, and re-expression of SAT1 in U2SURP-silencing cells partially rescued the impaired malignant phenotypes of TNBC cells caused by U2SURP knockdown both in vitro and in mice. The MYC-U2SURP-SAT1 signaling axis is a potential target in the treatment of TNBC.

Keywords: Cap-dependent translation; SR protein; Splicing switch; Therapeutic target; Transcription regulation

DOI: https://doi.org/10.1016/j.canlet.2023.216124