bims-polyam 2022-04-17 papers

Issue of 2022–04–17
five papers selected by
Sebastian J. Hofer, University of Graz

Int J Mol Sci. 2022 Mar 29. pii: 3752. [Epub ahead of print]23(7):

A Second Gamma-Glutamylpolyamine Synthetase, GlnA2, Is Involved in Polyamine Catabolism in Streptomyces coelicolor.

Sergii Krysenko, Nicole Okoniewski, Merle Nentwich, Arne Matthews, Moritz Bäuerle, Alina Zinser, Tobias Busche, Andreas Kulik, Stephanie Gursch, Annika Kemeny, Agnieszka Bera, Wolfgang Wohlleben.

Streptomyces coelicolor is a soil bacterium living in a habitat with very changeable nutrient availability. This organism possesses a complex nitrogen metabolism and is able to utilize the polyamines putrescine, cadaverine, spermidine, and spermine and the monoamine ethanolamine. We demonstrated that GlnA2 (SCO2241) facilitates S. coelicolor to survive under high toxic polyamine concentrations. GlnA2 is a gamma-glutamylpolyamine synthetase, an enzyme catalyzing the first step in polyamine catabolism. The role of GlnA2 was confirmed in phenotypical studies with a glnA2 deletion mutant as well as in transcriptional and biochemical analyses. Among all GS-like enzymes in S. coelicolor, GlnA2 possesses the highest specificity towards short-chain polyamines (putrescine and cadaverine), while its functional homolog GlnA3 (SCO6962) prefers long-chain polyamines (spermidine and spermine) and GlnA4 (SCO1613) accepts only monoamines. The genome-wide RNAseq analysis in the presence of the polyamines putrescine, cadaverine, spermidine, or spermine revealed indication of the occurrence of different routes for polyamine catabolism in S. coelicolor involving GlnA2 and GlnA3. Furthermore, GlnA2 and GlnA3 are differently regulated. From our results, we can propose a complemented model of polyamine catabolism in S. coelicolor, which involves the gamma-glutamylation pathway as well as other alternative utilization pathways.

Keywords: GS-like enzymes; GlnA; GlnA2; GlnA3; Streptomyces coelicolor; nitrogen assimilation; polyamine catabolism

DOI: https://doi.org/10.3390/ijms23073752

J Chromatogr A. 2022 Apr 05. pii: S0021-9673(22)00216-3. [Epub ahead of print]1671 463021

Liquid chromatography-tandem mass spectrometry based quantification of arginine metabolites including polyamines in different sample matrices.

Mathias Langner, Ivona Mateska, Nicole Bechmann, Ben Wielockx, Triantafyllos Chavakis, Vasileia Ismini Alexaki, Mirko Peitzsch.

The conditionally essential amino acid arginine and its metabolic products play an important role in different biological processes, such as metabolic regulation of the immune response, including macrophage activation and polarization and regulation of T cell function. Furthermore, the polyamine spermidine has a role in aging and age-related diseases. Additionally, altered polyamine metabolism may be associated with neurodegenerative diseases, while polyamine levels may present useful biomarkers associated with severity of Parkinson's disease or with progression of non-alcoholic fatty liver disease. In the present study, a simple, derivatization-free hydrophilic interaction liquid chromatography based tandem mass spectrometry (LC-MS/MS) method is described, that allows the accurate quantification of arginine and related amine, polyamine and acetylated polyamine metabolites in different experimental sample matrices, such as cell lysates, cell culture supernatants and tissues. Ten arginine metabolites, including citrulline, agmatine, ornithine, putrescine, spermidine, spermine, N1-acetylspermidine, N1-acetylspermine, N1,N12-diacetylspermine and arginine in conjunction with the metabolic cofactors S-adenosylhomocysteine and S-adenosylmethionine are simultaneously analyzed within a total LC-MS/MS run time of 9.5 min. The assay is suitable to quantify concentration ranges over multiple orders of magnitude for all metabolites with averaged accuracies observed at 103.2% ± 6.8%, 99.0% ± 4.2% and 100.4% ± 4.3% in cell lysates, cell culture supernatant and tissue extracts, respectively. Inter-day coefficients of variation ranged from 5.9 to 14.8% in cell lysates, 6.7 to 14.6% in cell culture supernatants and 5.3 to 12.0% in tissue extracts. The method was successfully applied to cell culture systems of different origin as well as different murine tissues and organs. The herein described LC-MS/MS method provides a simple tool for a fast and simultaneous analysis of arginine metabolites, including polyamines and their respective metabolic cofactors. Assay performance characteristics demonstrate suitability for applications in different experimental and preclinical settings.

Keywords: Arginine metabolites; LC-MS/MS; Polyamines

DOI: https://doi.org/10.1016/j.chroma.2022.463021

Elife. 2022 Apr 13. pii: e77704. [Epub ahead of print]11

Free spermidine evokes superoxide radicals that manifest toxicity.

Vineet Kumar, Rajesh Kumar Mishra, Debarghya Ghose, Arunima Kalita, Pulkit Dhiman, Anand Prakash, Nirja Thakur, Gopa Mitra, Vinod D Chaudhari, Amit Arora, Dipak Dutta.

Spermidine and other polyamines alleviate oxidative stress, yet excess spermidine seems toxic to Escherichia coli unless it is neutralized by SpeG, an enzyme for the spermidine N-acetyl transferase function. Thus, wild-type E. coli can tolerate applied exogenous spermidine stress, but DspeG strain of E. coli fails to do that. Here, using different ROS probes and performing electron paramagnetic resonance spectroscopy, we provide evidence that although spermidine mitigates oxidative stress by lowering overall ROS levels, excess of it simultaneously triggers the production of superoxide radicals, thereby causing toxicity in the DspeG strain. Furthermore, performing microarray experiment and other biochemical assays, we show that the spermidine-induced superoxide anions affected redox balance and iron homeostasis. Finally, we demonstrate that while RNA-bound spermidine inhibits iron oxidation, free spermidine interacts and oxidizes the iron to evoke superoxide radicals directly. Therefore, we propose that the spermidine-induced superoxide generation is one of the major causes of spermidine toxicity in E. coli.

Keywords: E. coli; biochemistry; chemical biology; chromosomes; gene expression

DOI: https://doi.org/10.7554/eLife.77704

Nutrients. 2022 Mar 27. pii: 1394. [Epub ahead of print]14(7):

Effect of Serum Spermidine on the Prognosis in Patients with Acute Myocardial Infarction: A Cohort Study.

Zhecong Yu, Yundi Jiao, Jin Zhang, Qianyi Xu, Jiahui Xu, Ruixue Li, Wei Yuan, Hui Guo, Zhaoqing Sun, Liqiang Zheng.

BACKGROUND: Spermidine, a natural polyamine, was found critically involved in cardioprotection and lifespan extension from both animal experiments and human studies.
AIMS: This study aimed to evaluate the effect of serum spermidine levels on the prognosis in patients with acute myocardial infarction (AMI) and investigate the potential mediation effect of oxidative stress in the above relationship.
METHODS: We included 377 patients with AMI in a prospective cohort study and measured serum spermidine and oxidative stress indexes (superoxide dismutase enzymes, glutathione peroxidase, and Malondialdehyde) using high-performance liquid chromatography with fluorescence detector and enzyme-linked immunosorbent assay, respectively. The associations of spermidine with AMI outcomes were evaluated using Cox proportional hazards models.
RESULTS: 84 (22.3%) major adverse cardiac events (MACE) were documented during a mean follow-up of 12.3 ± 4.2 months. After multivariable adjustment, participants with serum spermidine levels of ≥15.38 ng/mL (T3) and 7.59-5.38 ng/mL (T2) had hazard ratio (HR) for recurrent AMI of 0.450 [95% confidence interval (CI): 0.213-0.984] and 0.441 (95% CI: 0.215-0.907) compared with the ≤7.59 ng/mL (T1), respectively. Participants in T3 and T2 had HR for MACE of 0.566 (95% CI: 0.329-0.947) and 0.516 (95% CI: 0.298-0.893) compared with T1. A faint J-shaped association was observed between serum spermidine levels and the risk of MACE (p-nonlinearity = 0.036). Comparisons of areas under receiver operator characteristics curves confirmed that a model including serum spermidine levels had greater predictive power than the one without it (0.733 versus 0.701, p = 0.041). A marginal statistically significant mediation effect of superoxide dismutase was shown on the association between spermidine and MACE (p = 0.091).
CONCLUSIONS: Serum spermidine was associated with an improved prognosis in individuals with AMI, whereas the underlying mechanism mediated by oxidative stress was not found.

Keywords: major adverse cardiac events; mediation analysis; oxidative stress; prognosis; spermidine

DOI: https://doi.org/10.3390/nu14071394

Front Plant Sci. 2022 ;13 783597

Polyamine: A Potent Ameliorator for Plant Growth Response and Adaption to Abiotic Stresses Particularly the Ammonium Stress Antagonized by Urea.

Song Sheng, Changzheng Wu, Yucheng Xiang, Wenxuan Pu, Shuhui Duan, Pingjun Huang, Xiaoyuan Cheng, Yuanyong Gong, Yilong Liang, Laihua Liu.

Polyamine(s) (PA, PAs), a sort of N-containing and polycationic compound synthesized in almost all organisms, has been recently paid considerable attention due to its multifarious actions in the potent modulation of plant growth, development, and response to abiotic/biotic stresses. PAs in cells/tissues occur mainly in free or (non- or) conjugated forms by binding to various molecules including DNA/RNA, proteins, and (membrane-)phospholipids, thus regulating diverse molecular and cellular processes as shown mostly in animals. Although many studies have reported that an increase in internal PA may be beneficial to plant growth under abiotic conditions, leading to a suggestion of improving plant stress adaption by the elevation of endogenous PA via supply or molecular engineering of its biosynthesis, such achievements focus mainly on PA homeostasis/metabolism rather than PA-mediated molecular/cellular signaling cascades. In this study, to advance our understanding of PA biological actions important for plant stress acclimation, we gathered some significant research data to succinctly describe and discuss, in general, PA synthesis/catabolism, as well as PA as an internal ameliorator to regulate stress adaptions. Particularly, for the recently uncovered phenomenon of urea-antagonized NH4 +-stress, from a molecular and physiological perspective, we rationally proposed the possibility of the existence of PA-facilitated signal transduction pathways in plant tolerance to NH4 +-stress. This may be a more interesting issue for in-depth understanding of PA-involved growth acclimation to miscellaneous stresses in future studies.

Keywords: G-protein-coupled receptor; abiotic stress; ammonium stress; lipid signaling; polyamine and arginine; urea signal

DOI: https://doi.org/10.3389/fpls.2022.783597