bims-polyam 2021-12-12 papers

bims-polyam

Biomed News

on Polyamines

Issue of 2021–12–12
seven papers selected by
Sebastian J. Hofer, University of Graz

New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases.
The Association Between Concentrations of Arginine, Ornithine, Citrulline and Major Depressive Disorder: A Meta-Analysis.
Spermidine Is Critical for Growth, Development, Environmental Adaptation, and Virulence in Fusarium graminearum.
Arabidopsis N-acetyltransferase activity 2 preferentially acetylates 1,3-diaminopropane and thialysine.
Stabilization of Ribosomal RNA of the Small Subunit by Spermidine in Staphylococcus aureus.
Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation.
Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in doxorubicin-induced apoptosis in rat cardiac myocytes.

Aging Dis. 2021 Dec;12(8): 1948-1963

New Insights into the Roles and Mechanisms of Spermidine in Aging and Age-Related Diseases.

Yu-Qing Ni, You-Shuo Liu.

  High incidences of morbidity and mortality associated with age-related diseases among the elderly population are a socio-economic challenge. Aging is an irreversible and inevitable process that is a risk factor for pathological progression of diverse age-related diseases. Spermidine, a natural polyamine, plays a critical role in molecular and cellular interactions involved in various physiological and functional processes. Spermidine has been shown to modulate aging, suppress the occurrence and severity of age-related diseases, and prolong lifespan. However, the precise mechanisms through which spermidine exerts its anti-aging effects have not been established. In this review, we elucidate on the mechanisms and roles underlying the beneficial effects of spermidine in aging from a molecular and cellular perspective. Moreover, we provide new insights into the promising potential diagnostic and therapeutic applications of spermidine in aging and age-related diseases.

Keywords:  age-related diseases; aging; autophagy; longevity; spermidine

DOI:  https://doi.org/10.14336/AD.2021.0603
Front Psychiatry. 2021 ;12 686973

The Association Between Concentrations of Arginine, Ornithine, Citrulline and Major Depressive Disorder: A Meta-Analysis.

Mingyue Fan, Xiao Gao, Li Li, Zhongyu Ren, Leanna M W Lui, Roger S McIntyre, Kayla M Teopiz, Peng Deng, Bing Cao.

  Alterations in the peripheral (e.g., serum, plasma, platelet) concentrations of arginine and its related catabolic products (i.e., ornithine, citrulline) in the urea and nitric oxide cycles have been reported to be associated with major depressive disorder (MDD). The meta-analysis herein aimed to explore the association between the concentration of peripheral arginine, its catabolic products and MDD, as well as to discuss the possible role of arginine catabolism in the onset and progression of MDD. PubMed, EMBASE, PsycINFO and Web of Science were searched from inception to June 2020. The protocol for the meta-analysis herein has been registered at the Open Science Framework [https://doi.org/10.17605/osf.io/7fn59]. In total, 745 (47.5%) subjects with MDD and 823 (52.5%) healthy controls (HCs) from 13 articles with 16 studies were included. Fifteen of the included studies assessed concentrations of peripheral arginine, eight assessed concentrations of ornithine, and six assessed concentrations of citrulline. Results indicated that: (1) the concentrations of arginine, ornithine, and citrulline were not significantly different between individuals with MDD and HCs when serum, plasma and platelet are analyzed together, (2) in the subgroups of serum samples, the concentrations of arginine were lower in individuals with MDD than HCs, and (3) concurrent administration of psychotropic medications may be a confounding variable affecting the concentrations of arginine, ornithine, and citrulline. Our findings herein do not support the hypothesis that arginine catabolism between individuals with MDD and HCs are significantly different. The medication status and sample types should be considered as a key future research avenue for assessing arginine catabolism in MDD.

Keywords:  arginine; bipolar disorder; catabolism; cognition; depression; metabolism; nitric oxide

DOI:  https://doi.org/10.3389/fpsyt.2021.686973
Front Microbiol. 2021 ;12 765398

Spermidine Is Critical for Growth, Development, Environmental Adaptation, and Virulence in Fusarium graminearum.

Guangfei Tang, Haoxue Xia, Jingting Liang, Zhonghua Ma, Wende Liu.

  Putrescine, spermidine, and spermine are the most common natural polyamines. Polyamines are ubiquitous organic cations of low molecular weight and have been well characterized for the cell function and development processes of organisms. However, the physiological functions of polyamines remain largely obscure in plant pathogenic fungi. Fusarium graminearum causes Fusarium head blight (FHB) and leads to devastating yield losses and quality reduction by producing various kinds of mycotoxins. Herein, we genetically analyzed the gene function of the polyamine biosynthesis pathway and evaluated the role of the endogenous polyamines in the growth, development, and virulence of F. graminearum. Our results found that deletion of spermidine biosynthesis gene FgSPE3 caused serious growth defects, reduced asexual and sexual reproduction, and increased sensitivity to various stresses. More importantly, ΔFgspe3 exhibited significantly decreased mycotoxin deoxynivalenol (DON) production and weak virulence in host plants. Additionally, the growth and virulence defects of ΔFgspe3 could be rescued by exogenous application of 5 mM spermidine. Furthermore, RNA-seq displayed that FgSpe3 participated in many essential biological pathways including DNA, RNA, and ribosome synthetic process. To our knowledge, these results indicate that spermidine is essential for growth, development, DON production, and virulence in Fusarium species, which provides a potential target to control FHB.

Keywords:  DON (deoxynivalenol); Fusarium graminearum; polyamine biosynthesis; spermidine; virulence

DOI:  https://doi.org/10.3389/fmicb.2021.765398
Plant Physiol Biochem. 2021 Nov 24. pii: S0981-9428(21)00592-1. [Epub ahead of print]170 123-132

Arabidopsis N-acetyltransferase activity 2 preferentially acetylates 1,3-diaminopropane and thialysine.

Roberto Mattioli, Gianmarco Pascarella, Riccardo D'Incà, Alessandra Cona, Riccardo Angelini, Veronica Morea, Paraskevi Tavladoraki.

  Polyamine acetylation has an important regulatory role in polyamine metabolism. It is catalysed by GCN5-related N-acetyltransferases, which transfer acetyl groups from acetyl-coenzyme A to the primary amino groups of spermidine, spermine (Spm), or other polyamines and diamines, as was shown for the human Spermidine/Spermine N1-acetyltransferase 1 (HsSSAT1). SSAT homologues specific for thialysine, a cysteine-derived lysine analogue, were also identified (e.g., HsSSAT2). Two HsSSAT1 homologues are present in Arabidopsis, namely N-acetyltransferase activity (AtNATA) 1 and 2. AtNATA1 was previously shown to be specific for 1,3-diaminopropane, ornithine, putrescine and thialysine, rather than Spm and spermidine. In the present study, in an attempt to find a plant Spm-specific SSAT, AtNATA2 was expressed in a heterologous bacterial system and catalytic properties of the recombinant protein were determined. Data indicate that recombinant AtNATA2 preferentially acetylates 1,3-diaminopropane and thialysine, throwing further light on AtNATA1 substrate specificity. Structural analyses evidenced that the preference of AtNATA1, AtNATA2 and HsSSAT2 for short amine substrates can be ascribed to different main-chain conformation or substitution of HsSSAT1 residues interacting with Spm distal regions. Moreover, gene expression studies evidenced that AtNATA1 gene, but not AtNATA2, is up-regulated by cytokinins, thermospermine and Spm, suggesting the existence of a link between AtNATAs and N1-acetyl-Spm metabolism. This study provides insights into polyamine metabolism and structural determinants of substrate specificity of non Spm-specific SSAT homologues.

Keywords:  1,3-Diaminopropane; AtNATA; N-acetyltransferases; Polyamines; SSAT; Spermine; Thialysine

DOI:  https://doi.org/10.1016/j.plaphy.2021.11.034
Front Mol Biosci. 2021 ;8 738752

Stabilization of Ribosomal RNA of the Small Subunit by Spermidine in Staphylococcus aureus.

Margarita Belinite, Iskander Khusainov, Heddy Soufari, Stefano Marzi, Pascale Romby, Marat Yusupov, Yaser Hashem.

  Cryo-electron microscopy is now used as a method of choice in structural biology for studying protein synthesis, a process mediated by the ribosome machinery. In order to achieve high-resolution structures using this approach, one needs to obtain homogeneous and stable samples, which requires optimization of ribosome purification in a species-dependent manner. This is especially critical for the bacterial small ribosomal subunit that tends to be unstable in the absence of ligands. Here, we report a protocol for purification of stable 30 S from the Gram-positive bacterium Staphylococcus aureus and its cryo-EM structures: in presence of spermidine at a resolution ranging between 3.4 and 3.6 Å and in its absence at 5.3 Å. Using biochemical characterization and cryo-EM, we demonstrate the importance of spermidine for stabilization of the 30 S via preserving favorable conformation of the helix 44.

Keywords:  RNA stability; Staphylococcus aureus; ribosomal RNA; ribosome 70 S; translation

DOI:  https://doi.org/10.3389/fmolb.2021.738752
Biofactors. 2021 Dec 09.

Regulation of citrulline synthesis in human enterocytes: Role of hypoxia and inflammation.

Morgane Couchet, Sandie Pestour, Charlotte Breuillard, Christelle Corne, John Rendu, Eric Fontaine, Christophe Moinard.

  Intensive care unit patients and chronic airway inflammatory disease are characterized by chronic systemic hypoxia and inflammation inducing a decrease in nitric oxide release due to impaired l-arginine (ARG) homeostasis. As ARG is synthesized from circulating l-citrulline (CIT), an alteration of CIT production in small intestine by ornithine carbamoyltransferase could be involved. Here, we posit that hypoxia and/or inflammation has effects on ornithine carbamoyltransferase regulation in enterocytes. A duodenal explant incubation model was used. Biopsy specimens taken from 25 selected patients were incubated for 6 h in 4 groups: control, inflammation, hypoxia, and hypoxia + inflammation. At the end of the incubation period, we measured CIT concentration in culture media, ornithine carbamoyltransferase activity, ornithine carbamoyltransferase protein and gene expression, protein expression of enzymes involved in the CIT production pathway, and expression of energy status proteins. Inflammation and/or hypoxia conditions did not affect CIT production. Ornithine carbamoyltransferase activity was increased in hypoxia conditions (p = 0.023). Expression of enzymes implicated in the CIT crossroads pathway and enzymes reflecting energy status variation was not affected by inflammation and hypoxia. Data sets were pooled to evaluate the variability of the four quartiles for each parameter. CIT production was found to increase over the quartiles whereas other parameters remained stable. Our results showed that intestinal CIT production is preserved during inflammation and/or hypoxia, thus confirming the significance of this metabolic pathway. This suggests that the CIT deficiency observed in clinical hypercatabolic states could be a consequence of high utilization for ARG synthesis.

Keywords:  amino acid; duodenum; metabolism; ornithine carbamoyltransferase; sepsis

DOI:  https://doi.org/10.1002/biof.1810
Int J Cardiol. 2021 Dec 02. pii: S0167-5273(21)01975-6. [Epub ahead of print]

Oxidative stress-responsive apoptosis inducing protein (ORAIP) plays a critical role in doxorubicin-induced apoptosis in rat cardiac myocytes.

Takako Yao, Tsutomu Fujimura, Kimie Murayama, Ko Okumura, Yoshinori Seko.

   BACKGROUND: Oxidative stress is implicated in the pathogenesis of doxorubicin-induced apoptosis in cardiac myocytes. However, the precise mechanism remains uncertain. We identified an apoptosis-inducing humoral factor, in a conditioned medium from cardiac myocytes subjected to hypoxia/reoxygenation, to be 69th tyrosine-sulfated eukaryotic translation initiation factor 5A (eIF5A). We named this novel secreted form of eIF5A, Oxidative stress-Responsive Apoptosis Inducing Protein (ORAIP). We confirmed that ischemia/reperfusion, ultraviolet-irradiation, and ionizing radiation significantly increased plasma levels of ORAIP in vivo, supporting that secretion of ORAIP is specific to the oxidative stress. To investigate the role of ORAIP in doxorubicin-induced apoptosis of cardiac myocytes.
METHODS: We analyzed plasma levels of ORAIP in rats treated with doxorubicin (10 mg/Kg) in vivo, and the effects of neutralizing anti-ORAIP monoclonal antibody (mAb) on doxorubicin-induced apoptosis of cardiac myocytes in vitro.
RESULTS: The (mean ± SE) plasma ORAIP levels before doxorubicin administration were (13.7 ± 2.7) ng/mL, they markedly increased with peak levels ([178.6 ± 6.5] ng/mL, p < 0.00001, vs. before administration) at 20 to 60 min after doxorubicin administration, then gradually decreased to (118.0 ± 4.8) ng/mL at 120 min. Treatment with a neutralizing anti-ORAIP mAb significantly (nearly 50%) suppressed doxorubicin-induced apoptosis of cardiac myocytes.
CONCLUSIONS: These data indicate that doxorubicin induces oxidative stress resulting in the strong expression of ORAIP in cardiac myocytes and marked secretion of ORAIP into peripheral circulation. This strongly suggests that ORAIP can be a novel sensitive biomarker as well as a possible therapeutic target for doxorubicin-induced cell injury in anti-cancer therapy.

Keywords:  Apoptosis; Cardiac myocytes; Doxorubicin; Eukaryotic translation initiation factor 5A (eIF5A); Oxidative stress; Oxidative stress-responsive apoptosis inducing protein (ORAIP)

DOI:  https://doi.org/10.1016/j.ijcard.2021.11.085