bims-polyam 2020-04-19 papers

on Polyamines

Issue of 2020–04–19
eight papers selected by
Sebastian J. Hofer, University of Graz and Alexander Ivanov, Engelhardt Institute of Molecular Biology

Exogenous spermine attenuates myocardial fibrosis in diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress and the canonical Wnt signaling pathway.
Chitosan and spermine enhance drought resistance in white clover, associated with changes in endogenous phytohormones and polyamines, and antioxidant metabolism.
SpeG polyamine acetyltransferase enzyme from Bacillus thuringiensis forms a dodecameric structure and exhibits high catalytic efficiency.
Enhancing antioxidant systems by exogenous spermine and spermidine in wheat (Triticum aestivum) seedlings exposed to salt stress.
Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats.
Molecular background of cadmium tolerance in Rht dwarf wheat mutant is related to a metabolic shift from proline and polyamine to phytochelatin synthesis.
Exogenous spermidine enhances the photosynthetic and antioxidant capacity of rice under heat stress during early grain-filling period.
Treatment With Lipopolysaccharide Induces Distinct Changes in Metabolite Profile and Body Weight in 129Sv and Bl6 Mouse Strains.

Cell Biol Int. 2020 Apr 13.

Exogenous spermine attenuates myocardial fibrosis in diabetic cardiomyopathy by inhibiting endoplasmic reticulum stress and the canonical Wnt signaling pathway.

Jing Hu, Xiaoxiao Lu, Xinying Zhang, Xiaoting Shao, Yuehong Wang, Junting Chen, Bingbing Zhao, Siwei Li, Changqing Xu, Can Wei.

  Myocardial fibrosis is one of the main pathological manifestations of diabetic cardiomyopathy (DCM). Spermine (SPM), a product of polyamine metabolism, plays an important role in many cardiac diseases including hypertrophy, ischemia, and infarction, but its role in diabetic myocardial fibrosis has not been clarified. This study aimed to investigate the role of polyamine metabolism, specifically SPM, in diabetic myocardial fibrosis and to explore the related mechanisms. We used intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) in Wistar rats and high glucose (HG, 40 mM) stimulated cardiac fibroblasts (CFs) to established a type 1 diabetes (T1D) model in vivo and in vitro, which were pretreated with exogenous SPM (5 mg/kg per day and 5 μM). The results showed that hyperglycemia induced the expression of the key polyamine synthesis enzyme ornithine decarboxylase (ODC) decreased and the key catabolic enzyme spermidine/spermine N1 -acetyltransferase (SSAT) increased compared with those in the control group. The body weight, blood insulin level, and cardiac ejection function were decreased, while blood glucose, heart weight, the ratio of heart weight to body weight, myocardial interstitial collagen deposition, and endoplasmic reticulum stress (ERS)-related protein (glucose-regulated protein-78, glucose-regulated protein-94, activating transcription factor-4, and C/EBP homology protein) expression in the T1D group were all significantly increased. HG also caused an increased expression of Wnt3, β-catenin (in cytoplasm and nucleus), while Axin2 and phosphorylated β-catenin decreased. Exogenous SPM improved the above changes caused by polyamine metabolic disorders. In conclusion, polyamine metabolism disorder occurs in the myocardial tissue of diabetic rats, causing myocardial fibrosis and ERS. Exogenous SPM plays a myocardial protective role via inhibiting of ERS and the canonical Wnt/β-catenin signaling pathway.

Keywords:  Wnt; diabetic cardiomyopathy; endoplasmic reticulum stress; myocardial fibrosis; spermine

DOI:  https://doi.org/10.1002/cbin.11360
Funct Plant Biol. 2018 Nov;45(12): 1205-1222

Chitosan and spermine enhance drought resistance in white clover, associated with changes in endogenous phytohormones and polyamines, and antioxidant metabolism.

Yan Zhang, Zhou Li, Ya-Ping Li, Xin-Quan Zhang, Xiao Ma, Lin-Kai Huang, Yan-Hong Yan, Yan Peng.

The interaction of chitosan and polyamines (PAs) could be involved mitigating drought stress in white clover (Trifolium repens L.). This research aimed to determine the effect of chitosan and PAs, and co-application of chitosan and PAs on improving drought tolerance associated with growth, phytohormones, polyamines and antioxidant metabolism. Plants were pretreated with or without 1gL-1 chitosan, 0.5mM spermine, or 1gL-1 chitosan+0.5mM spermine, then subjected to drought induced by polyethylene glycol (PEG) 6000 (-0.5MPa) in growth chambers for 14 days. Exogenous chitosan and spermine improved the level of PAs by regulating arginine decarboxylases, S-adenosyl methionine decarboxylase, copper-containing amine oxidase and polyamine oxidase activity, and expression of the genes encoding these enzymes under drought. Application of exogenous chitosan improved ABA content under normal and drought conditions. In addition, chitosan and spermine significantly enhanced the levels of cytokinin and GA, but reduced IAA levels during drought stress. Exogenous chitosan and spermine improved antioxidant defence, including enzyme activity, gene expression and the content of ascorbate and glutathione compounds, leading to a decline in superoxide anion radicals, H2O2 and malondialdehyde, effectively mitigating drought-induced oxidative damage. Other protective metabolites, such as total phenols and flavonoids, increased considerably under application of chitosan and spermine. These results suggest that chitosan-induced drought tolerance could be involved in PA metabolism, changes in endogenous phytohormones and antioxidant defence in white clover. Co-application of chitosan and spermine was more effective than either chitosan or spermine alone in mitigating drought stress.

DOI: https://doi.org/10.1071/FP18012
J Struct Biol. 2020 Apr 10. pii: S1047-8477(20)30075-7. [Epub ahead of print] 107506

SpeG polyamine acetyltransferase enzyme from Bacillus thuringiensis forms a dodecameric structure and exhibits high catalytic efficiency.

Sofiya Tsimbalyuk, Aleksander Shornikov, Van Thi Bich Le, Misty L Kuhn, Jade K Forwood.

  Polyamines are important for regulating biofilms and the exopolysaccharide of the biofilm matrix of Bacillus subtilis. Understanding how enzymes can regulate polyamine concentrations is critical for learning more about how these processes occur in diverse bacteria. Here, we describe the structure and function of another member of the spermidine/spermine acetyltransferases (SSAT) found in Bacilli. The SpeG enzyme from B. thuringiensis (BtSpeG) binds polyamines in its allosteric site and adopts a dodecameric oligomeric state similar to other SpeG enzymes from Gram-negative bacteria. Our kinetic results show the catalytic efficiency of BtSpeG was greater than any previously characterized SpeG to date, and in contrast to other SpeG proteins it exhibited very similar kinetic properties toward both spermine and spermidine. Similar to the SpeG enzyme from E. coli, BtSpeG was able to acetylate spermidine on the N1 and N8 positions. The turnover of BtSpeG toward spermine and spermidine was also two to three orders of magnitude greater than any other Bacilli SSAT enzyme that has been previously characterized. SpeG proteins from Bacilli, including B. cereus, B. thuringiensis and B. anthracis share nearly identical sequences and therefore our results likely provide insight into the structure/function relationship across multiple Bacillus species.

Keywords:  SpeG; acetyltransferase; dodecameric; x-ray crystallography, polyamine, Bacillus

DOI:  https://doi.org/10.1016/j.jsb.2020.107506
Funct Plant Biol. 2018 Jun;45(7): 745-759

Enhancing antioxidant systems by exogenous spermine and spermidine in wheat (Triticum aestivum) seedlings exposed to salt stress.

Abdelaleim I ElSayed, Mohammed S Rafudeen, Mohamed A M El-Hamahmy, Dennis C Odero, M Sazzad Hossain.

Plants have evolved complex mechanisms to mitigate osmotic and ionic stress caused by high salinity. The effect of exogenous spermine (Spm) and spermidine (Spd) on defence responses of wheat seedlings under NaCl stress was investigated by measuring antioxidant enzyme activities and the transcript expression of corresponding genes. Exogenous Spm and Spd decreased the level of malondialdehyde, increased chlorophyll and proline contents, and modulated PSII activity in wheat seedlings under salt stress. Spermidine alleviated negative effects on CO2 assimilation induced by salt stress in addition to significantly increasing the activity and content of ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco). It appears Spd conferred salinity tolerance in wheat seedlings by enhancing photosynthetic capacity through regulation of gene expression and the activity of key CO2 assimilation enzymes. Exogenous Spm regulated activities of different antioxidant enzymes (catalase, glutathione reductase, dehydroascorbate reductase, ascorbate peroxidase, and superoxide dismutase) and efficiently modulate their transcription levels in wheat seedlings under salt stress. It is likely that Spm plays a key role in alleviating oxidative damage of salt stress by adjusting antioxidant enzyme activities in plants. In addition, exogenous Spd increased transcript level of spermine synthase under salt stress. Salinity stress also caused an increase in transcript levels of diamine oxidase (DAO) and polyamine oxidase (PAO). Exogenous Spd application resulted in a marked increase in free Spd and Spm contents under saline conditions. These results show that exogenous Spd and Spm effectively upregulated transcriptional levels of antioxidant enzyme genes and improved the defence response of plants under salt stress.

DOI: https://doi.org/10.1071/FP17127
Geroscience. 2020 Apr 13.

Long-term treatment with spermidine increases health span of middle-aged Sprague-Dawley male rats.

Madalina Filfan, Andrei Olaru, Ion Udristoiu, Claudiu Margaritescu, Eugen Petcu, Dirk M Hermann, Aurel Popa-Wagner.

  Let alone calorie restriction, life span extension in higher organisms has proven to be difficult to achieve using simple drugs. Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. However, younger subjects (< 40 years of age) are infrequently prescribed nor self-medicating with antiaging drugs. Therefore, in the present study, we aimed at assessing the effect of long-term treatment with spermidine given in the drinking water on behavioral performance and longevity of male, middle-aged Sprague-Dawley rats. We report that spermidine given in the drinking water did not extend neither the median nor the maximum life span of the middle-aged male Sprague-Dawley rats. However, spermidine treatment had a beneficial effect on the body weight and the kidney tubules, liver, and heart morphology. Behaviorally, spermidine led to a reduction in anxiety and an increase in curiosity, as assessed by exploratory behavior. Moreover, long-term treatment with spermidine enhanced autophagy in the brain and led to a diminished expression of the inflammatory markers, Tgfb, CD11b, Fcgr1, Stat1, CR3, and GFAP mRNAs in several cortical region and hippocampus of the treated rats suggesting that one beneficial effect of the long-term treatment with spermidine is an attenuated proinflammatory state in the aged brain. Our results suggest that long-term treatment with spermidine increases health span of middle-aged rats by attenuating neuroinflammation and improving anxiety and exploratory behavior.

Keywords:  Autophagy; Behavior; Longevity; Middle-aged rats; Neuroinflammation; Spermidine

DOI:  https://doi.org/10.1007/s11357-020-00173-5
Environ Sci Pollut Res Int. 2020 Apr 15.

Molecular background of cadmium tolerance in Rht dwarf wheat mutant is related to a metabolic shift from proline and polyamine to phytochelatin synthesis.

Gabriella Szalai, Judit Tajti, Kamirán Áron Hamow, Denyicska Ildikó, Radwan Khalil, Radomira Vanková, Petr Dobrev, Svetlana P Misheva, Tibor Janda, Magda Pál.

  Plant height is among the most important agronomic traits influencing crop yield. Wheat lines carrying Rht genes are important in plant breeding due to their both higher yield capacity and better tolerance to certain environmental stresses. However, the effects of dwarf-inducing genes on stress acclimation mechanisms are still poorly understood. Under the present conditions, cadmium stress induced different stress responses and defence mechanisms in the wild-type and dwarf mutant, and the mutant with the Rht-B1c allele exhibited higher tolerance. In the wild type after cadmium treatment, the abscisic acid synthesis increased in the leaves, which in turn might have induced the polyamine and proline metabolisms in the roots. However, in the mutant line, the slight increment in the leaf abscisic acid content accompanied by relatively high salicylic acid accumulation was not sufficient to induce such a great accumulation of proline and putrescine. Although changes in proline and polyamines, especially putrescine, showed similar patterns, the accumulation of these compounds was antagonistically related to the phytochelatin synthesis in the roots of the wild type after cadmium stress. In the dwarf genotype, a favourable metabolic shift from the synthesis of polyamine and proline to that of phytochelatin was responsible for the higher cadmium tolerance observed.

Keywords:  ABA; PA; PCs; Proline; Rht; SA

DOI:  https://doi.org/10.1007/s11356-020-08661-z
Funct Plant Biol. 2018 Aug;45(9): 911-921

Exogenous spermidine enhances the photosynthetic and antioxidant capacity of rice under heat stress during early grain-filling period.

She Tang, Haixiang Zhang, Ling Li, Xia Liu, Lin Chen, Wenzhu Chen, Yanfeng Ding.

High temperature has adverse effects on rice growth by inhibiting the flag leaf photosynthetic and antioxidant capacity, which can be alleviated by various exogenous chemicals such as spermidine (Spd). However, the role of Spd in conferring heat tolerance in rice is not well documented. Conventional japonica rice varieties Wuyunjing 24 and Ningjing 3 were treated with high temperatures at 37.5/27.0°C (day/night) and foliar sprayed with 1mmolL-1 Spd after flowering. Results showed activities of superoxide dismutase (SOD) and peroxidase (POD) activities were deceased during high temperature treatment and eventually lead to the malondialdehyde (MDA) accumulation. Exogenous Spd significantly increased both SOD and POD activities at the later stage of high-temperature treatment, and reduced MDA accumulation were identified in both rice varieties. Application of Spd further increased the amount of soluble sugars during high temperature stress and that maintained the osmotic equilibrium of rice leaves. Spd significantly increased photosystem II (ΦPSII), photosynthetic electron transport rate (ETR), variable fluorescence/maximum fluorescence ratio (Fv'/Fm'), stomatal conductance and the photochemical reaction of light energy ratio (Pr), and ultimately improved the photosynthetic and transpiration rate during high temperature stress. In conclusion, exogenous Spd can effectively alleviate the adverse consequences of high temperature and could be further applied to provide strategies in mitigating the challenges of global warming-induced yield loss and other possible relevant issues.

DOI: https://doi.org/10.1071/FP17149
Front Pharmacol. 2020 ;11 371

Treatment With Lipopolysaccharide Induces Distinct Changes in Metabolite Profile and Body Weight in 129Sv and Bl6 Mouse Strains.

Maria Piirsalu, Egon Taalberg, Kersti Lilleväli, Li Tian, Mihkel Zilmer, Eero Vasar.

  Mouse strains differ significantly in their behaviors and responses to pathogenic and pharmacological agents. This study seeks to characterize behavioral and metabolomic profiles of two widely used mouse lines, 129S6/SvEvTac (129Sv) and C57BL/6NTac (Bl6), to acute administration of lipopolysaccharide (LPS). LPS caused a significant suppression of locomotor activity and a decline in body weight (BW) in both strains within 24 h. However, the BW loss was more pronounced in Bl6 than in 129Sv. Comparison of strains revealed clear differences between their metabolomic profiles. According to the general linear model analysis (GLM), the 1.5 h LPS challenge in Bl6 caused a decrease of propionylcarnitine (C3), glucogenic amino acids, and acetylornithine (Ac-Orn), whereas the response of 129Sv included decreased concentrations of short-chain acylcarnitines (SCACs), citrulline, and elevation of glycerophospholipid (PCaa C42:0) and sphingolipid [SM(OH)C16:1]. 24 h after LPS administration, robust alterations in lipid profile were observed in both strains. LPS treatment caused elevation of sphingolipids, phosphatidylcholine diacyls (PCaa) as well as a decrease in lysophosphatidylcholines (LysoPC). However, the number of elevated PCaa and sphingolipids was considerably higher in 129Sv. In addition to lipids, 24 h LPS challenge in Bl6 mice induced increased levels of kynurenine (KYN), putrescine and decreased levels of citrulline, hexoses, Ac-Orn, and PC acyl-alkyl (PCae 38:2) as well as severe BW loss. In contrast, the 24 h LPS challenge in 129Sv mice induced increased levels of KYN, long-chain acylcarnitines (LCACs) and decreased levels of citrulline as well as moderate BW loss. Altogether, our study revealed both similarities and differences in response to LPS in Bl6 and 129Sv strains. For major differences, Bl6 mice showed stronger reduction of BW 24 h after LPS treatment, accompanied by significantly reduced levels of hexoses, the ratio between LysoPC16:1/LysoPC16:0, and elevated levels of neuroprotective putrescine. In 129Sv mice, the BW loss was milder, accompanied by increased levels of hydroxylated LCACs, probably reflecting shifts in oxidative metabolism of fatty acids. One may suggest that LPS caused stronger hypometabolic state in the Bl6 mice than in the 129Sv strain. Altogether, this study confirms that Bl6 and 129Sv mice display vastly distinct adaptation capacities independent from the nature of stressful challenge.

Keywords:  129Sv strain; Bl6 strain; hypometabolism; inflammation; innate immunity; lipopolysaccharide; metabolic profiling

DOI:  https://doi.org/10.3389/fphar.2020.00371