bims-polyam 2023-08-20 papers

Issue of 2023–08–20
three papers selected by
Sebastian J. Hofer, University of Graz

JCI Insight. 2023 Aug 15. pii: e169308. [Epub ahead of print]

Modulating the polyamine-hypusine axis controls generation of CD8+ tissue resident memory T cells.

Aya G Elmarsafawi, Rebecca S Hesterberg, Mario R Fernandez, Chunying Yang, Lancia Nf Darville, Min Liu, John M Koomen, Otto Phanstiel Iv, Reginald Atkins, John E Mullinax, Shari A Pilon-Thomas, Frederick L Locke, Pearlie K Epling-Burnette, John L Cleveland.

Glutaminolysis is a hallmark of the activation and metabolic reprogramming of T cells. Isotopic tracer analyses of antigen-activated effector CD8+ T cells revealed that glutamine is the principal carbon source for the biosynthesis of polyamines putrescine, spermidine and spermine. These metabolites play critical roles in activation-induced T-cell proliferation, as well as for the production of hypusine, which is derived from spermidine and is covalently linked to the translation elongation factor eIF5A. Here, we demonstrated that the glutamine-polyamine-hypusine axis controls the expression of CD69, an important regulator of tissue resident memory T cells (TRM). Inhibition of this circuit augmented the development of TRM cells ex vivo and in vivo in the bone marrow, a well-established niche for TRM cells. Furthermore, blocking the polyamine-hypusine axis augmented CD69 expression and IFN-γ and TNF-α production in human CD8+ T cells from peripheral blood and sarcoma tumor infiltrating lymphocytes, as well as in human CD8+ CAR-T cells. Collectively, these findings support the notion that the polyamine-hypusine circuit can be exploited to modulate TRM cells for therapeutic benefit.

Keywords: Immunology; Metabolism; Polyamines; T cells

DOI: https://doi.org/10.1172/jci.insight.169308

Bioresour Technol. 2023 Aug 16. pii: S0960-8524(23)01116-1. [Epub ahead of print] 129688

The influence of spermidine on the build-up of fucoxanthin in Isochrysis sp. Acclimated to varying light intensities.

Yahui Bo, Shanshan Wang, Feifei Ma, Artem Yurevich Manyakhin, Guilin Zhang, Xiaohui Li, Chengxu Zhou, Baosheng Ge, Xiaojun Yan, Roger Ruan, Pengfei Cheng.

Spermidine is a type of important growth regulator, which involved in the biosynthesis of photosynthetic pigments, and has the function of promoting cell proliferation. In this study, Isochrysis sp. was selected as the research object to explore the effects of spermidine supplementation on the growth of algal cells and fucoxanthin synthesis under different light intensities. The results showed that the cell density (5.40 × 106 cells/mL) of algae were the highest at 11 days under the light intensity of 200 μmol·m-2·s-1 and spermidine content of 150 μM. The contents of diadinoxanthin (1.09 mg/g) and fucoxanthin (6.11 mg/g) were the highest when spermidine was added under low light intensity, and the growth of algal cells and fucoxanthin metabolism were the most significant. In the carotenoid synthesis pathway, PDS (phytoene desaturase) was up-regulated by 1.96 times and VDE (violaxanthin de-epoxidase) was down-regulated by 0.95 times, which may promote fucoxanthin accumulation.

Keywords: Fucoxanthin; Growth metabolism; Isochrysis sp.; Light intensity; Spermine; Transcriptome analysis

DOI: https://doi.org/10.1016/j.biortech.2023.129688

Nutr Metab Cardiovasc Dis. 2023 Jul 20. pii: S0939-4753(23)00295-8. [Epub ahead of print]

Effects of two-month treatment with a mixture of natural activators of autophagy on oxidative stress and arterial stiffness in patients with essential hypertension: A pilot study.

Giuliano Tocci, Giuseppe Biondi-Zoccai, Maurizio Forte, Giovanna Gallo, Giulia Nardoianni, Emiliano Fiori, Luca D'Ambrosio, Riccardo Di Pietro, Giulio Stefanini, Francesco Cannata, Erica Rocco, Beatrice Simeone, Gianmarco Sarto, Leonardo Schirone, Alessandra D'Amico, Mariangela Peruzzi, Cristina Nocella, Massimo Volpe, Speranza Rubattu.

BACKGROUND AND AIMS: Trehalose, spermidine, nicotinamide, and polyphenols are natural substances that exert pro-autophagic and antioxidant properties. Their role in blood pressure (BP) regulation and preservation of vascular function in essential hypertension is unknown. The aim of this study was to evaluate the effect of a mixture of these agents on BP level, markers of oxidative stress, autophagy, endothelial function, and vascular stiffness in outpatients with grade 1 uncomplicated essential hypertension.
METHODS AND RESULTS: A single-centre, open-label, case-control, pilot study was conducted in adult outpatients (aged ≥18 years) receiving or not the mixture for two months along with the standard therapies. Both at baseline and at the end of the treatment the following clinical parameters were evaluated: brachial seated office BP level, central aortic pressure, pulse wave velocity, augmentation index (AI@75). Both at baseline and at the end of the treatment, a blood sample was drawn for the measurement of: H2O2, HBA%, levels of sNOX2-dp, Atg 5, P62, endothelin 1, and NO bioavailability. The mixture of nutraceuticals did not influence BP levels. Patients receiving the mixture showed a significant decrease of oxidative stress, stimulation of autophagy, increased NO bioavailability and no increase of the AI@75, in contrast to what observed in hypertensive patients not receiving the mixture.
CONCLUSIONS: The supplementation of the trehalose, spermidine, nicotinamide, and polyphenols mixture counteracted hypertension-related arterial stiffness through mechanisms likely dependent on oxidative stress downregulation and autophagy stimulation. These natural activators of autophagy may represent favourable adjuvants for prevention of the hypertensive cardiovascular damage.

Keywords: Autophagy; Hypertension; Oxidative stress; Polyphenols; Trehalose; Vascular function

DOI: https://doi.org/10.1016/j.numecd.2023.07.026