Altered Brain Arginine Metabolism and Polyamine System in a P301S Tauopathy Mouse Model: A Time-Course Study

Altered arginine metabolism (including the polyamine system) has recently been implicated in the pathogenesis of tauopathies, characterised by hyperphosphorylated and aggregated microtubule-associated protein tau (MAPT) accumulation in the brain. The present study, for the first time, systematically determined the time-course of arginine metabolism changes in the MAPT P301S (PS19) mouse brain at 2, 4, 6, 8 and 12 months of age. The polyamines putrescine, spermidine and spermine are critically involved in microtubule assembly and stabilization. This study, therefore, further investigated how polyamine biosynthetic and catabolic enzymes changed in PS19 mice. There were general age-dependent increases of L-arginine, L-ornithine, putrescine and spermidine in the PS19 brain (particularly in the hippocampus and parahippocampal region). While this profile change clearly indicates a shift of arginine metabolism to favor polyamine production (a polyamine stress response), spermine levels were decreased or unchanged due to the upregulation of polyamine retro-conversion pathways. Our results further implicate altered arginine metabolism (particularly the polyamine system) in the pathogenesis of tauopathies. Given the role of the polyamines in microtubule assembly and stabilization, future research is required to understand the functional significance of the polyamine stress response and explore the preventive and/or therapeutic opportunities for tauopathies by targeting the polyamine system.     

Influence of Green,Red and Blue Light Emitting Diodes on Multiprotein Complex Proteins and Photosynthetic Activity under Different Light Intensities in Lettuce Leaves (Lactuca sativa L.)

The objective of this study was to investigate the response of light emitting diodes (LEDs) at different light intensities (70 and 80 for green LEDs, 88 and 238 for red LEDs and 80 and 238 μmol m⁻² s⁻¹ for blue LEDs) at three wavelengths in lettuce leaves. Lettuce leaves were exposed to (522 nm), red (639 nm) and blue (470 nm) LEDs of different light intensities. Thylakoid multiprotein complex proteins and photosynthetic metabolism were then investigated. Biomass and photosynthetic parameters increased with an increasing light intensity under blue LED illumination and decreased when illuminated with red and green LEDs with decreased light intensity. The expression of multiprotein complex proteins including PSII-core dimer and PSII-core monomer using blue LEDs illumination was higher at higher light intensity (238 μmol m⁻² s⁻¹) and was lowered with decreased light intensity (70–80 μmol m⁻² s⁻¹). The responses of chloroplast sub-compartment proteins, including those active in stomatal opening and closing, and leaf physiological responses at different light intensities, indicated induced growth enhancement upon illumination with blue LEDs. High intensity blue LEDs promote plant growth by controlling the integrity of chloroplast proteins that optimize photosynthetic performance in the natural environment.     

Polyamines Influence Mouse Sperm Channels Activity

Polyamines are ubiquitous polycationic compounds that are highly charged at physiological pH. While passing through the epididymis, sperm lose their capacity to synthesize the polyamines and, upon ejaculation, again come into contact with the polyamines contained in the seminal fluid, unleashing physiological events that improve sperm motility and capacitation. In the present work, we hypothesize about the influence of polyamines, namely, spermine, spermidine, and putrescine, on the activity of sperm channels, evaluating the intracellular concentrations of chloride [Cl⁻]i, calcium [Ca²⁺]i, sodium [Na⁺]i, potassium [K⁺]i, the membrane V_m, and pHi. The aim of this is to identify the possible regulatory mechanisms mediated by the polyamines on sperm-specific channels under capacitation and non-capacitation conditions. The results showed that the presence of polyamines did not directly influence the activity of calcium and chloride channels. However, the results suggested an interaction of polyamines with sodium and potassium channels, which may contribute to the membrane V_m during capacitation. In addition, alkalization of the pHi revealed the possible activation of sperm-specific Na⁺/H⁺ exchangers (NHEs) by the increased levels of cyclic AMP (cAMP), which were produced by soluble adenylate cyclase (sAC) and interact with the polyamines, evidence that is supported by in silico analysis.     

The Protective Function and Modification of Secondary Metabolite Accumulation in Response to Light Stress in Dracocephalum forrestii Shoots

The aim of this work was to determine the effect of stress conditions caused by different light sources, i.e., blue LED (λ = 430 nm), red LED (λ = 670 nm), blue and red LED (70%:30%) and white LED (430–670 nm) on the growth and morphology of cultivated in vitro Dracocephalum forrestii shoot culture. It also examines the effects on bioactive phenolic compound production and photosynthetic pigment content, as well as on antioxidant enzyme activity (CAT, SOD, POD) and antioxidant properties. The most beneficial proliferation effect was observed under white LEDs (7.1 ± 2.1 shoots per explant). The white and blue lights stimulated the highest fresh weight gain, while red light induced the highest dry weight gain. The total phenolic acid content ranged from 13.824 ± 1.181 to 20.018 ± 801 mg g DW⁻¹ depending on light conditions. The highest content of rosmarinic acid was found in the control shoots (cultivated under fluorescent lamps), followed by culture grown under red light. All LED treatments, especially red and blue, increased salvianolic acid B content, and blue increased apigenin p-coumarylrhamnoside biosynthesis. The greatest ferric reduction activity was observed in shoots cultivated under red light, followed by blue; this is associated with the presence of the highest total phenol content, especially phenolic acids. Similarly, the highest DPPH radical scavenging potential was observed under red light followed by blue. This study proves that LEDs have emerged as significant support for directed in vitro propagation, taking advantage of specific stress responses on various light spectra. This study also showed how stress induced by different LED light spectra increases in Dracocephalum forrestii the synthesis of pharmacologically-active compounds. Hence, light stress may turn out to be a simpler alternative to metabolic engineering for improving the production of secondary metabolites of therapeutic value.     

Effects of polyamine structure on rosin sizing under neutral papermaking conditions

The sizing effectiveness of rosin size with four typical polyamines, polyvinylamine (PVAm), polyallylamine (PAAm), poly(dimethylamino ethyl methacrylate) (PDMAEMA), and polyethyleneimine (PEI), was investigated under neutral papermaking conditions. The polyamines with linear structures were more effective than was PEI with a branched structure. The smaller the side chains of the linear polyamine, the larger was the sizing degree of the rosin emulsion size (RE) with the polyamine. The polyamine with smaller molecular geometric size could retain more rosin size on the pulp and form smaller rosin-polyamine complexes. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 65: 2159–2163, 1997     

Polyamines Metabolism Interacts with γ-Aminobutyric Acid,Proline and Nitrogen Metabolisms to Affect Drought Tolerance of Creeping Bentgrass

Due to increased global warming and climate change, drought has become a serious threat to horticultural crop cultivation and management. The purpose of this study was to investigate the effect of spermine (Spm) pretreatment on metabolic alterations of polyamine (PAs), γ-aminobutyric acid (GABA), proline (Pro), and nitrogen associated with drought tolerance in creeping bentgrass (Agrostis stolonifera). The results showed that drought tolerance of creeping bentgrass could be significantly improved by the Spm pretreatment, as demonstrated by the maintenance of less chlorophyll loss and higher photosynthesis, gas exchange, water use efficiency, and cell membrane stability. The Spm pretreatment further increased drought-induced accumulation of endogenous PAs, putrescine, spermidine, and Spm, and also enhanced PAs metabolism through improving arginine decarboxylases, ornithine decarboxylase, S-adenosylmethionine decarboxylase, and polyamine oxidase activities during drought stress. In addition, the Spm application not only significantly improved endogenous GABA content, glutamate content, activities of glutamate decarboxylase and α-ketoglutarase, but also alleviated decline in nitrite nitrogen content, nitrate reductase, glutamine synthetase, glutamate synthetase, and GABA aminotransferase activities under drought stress. The Spm-pretreated creeping bentgrass exhibited significantly lower ammonia nitrogen content and nitrite reductase activity as well as higher glutamate dehydrogenase activity than non-pretreated plants in response to drought stress. These results indicated beneficial roles of the Spm on regulating GABA and nitrogen metabolism contributing towards better maintenance of Tricarboxylic acid (TCA) cycle in creeping bentgrass. Interestingly, the Spm-enhanced Pro metabolism rather than more Pro accumulation could be the key regulatory mechanism for drought tolerance in creeping bentgrass. Current findings provide a comprehensive understanding of PAs interaction with other metabolic pathways to regulate drought tolerance in grass species.     

Balancing Damage via Non-Photochemical Quenching,Phenolic Compounds and Photorespiration in Ulva prolifera Induced by Low-Dose and Short-Term UV-B Radiation

The Yellow Sea green tide (YSGT) is the world’s largest transregional macroalgal blooms, and the causative species Ulva prolifera (U. prolifera) suffers from ultraviolet-b radiation (UVBR) during the floating migration process. Previous study confirmed that U. prolifera displayed a wide variety of physiological responses characterized as acclimation to UVBR, while the response mechanisms against low-dose and short-term radiation (LDSTR) are not clear. A study with photosynthetically active radiation (PAR) and UVBR was designed: normal light (NL: 72 μmol photons m⁻² s⁻¹), NL+0.3 (UVBR: 0.3 W·m⁻²), and NL+1.6 (UVBR: 1.6 W·m⁻²). The results showed that high-dose UVBR inhibited photosynthesis in thalli, especially under long-term exposure, while a variety of physiological responses were observed under LDSTR. The inhibition of photosynthesis appeared to be ameliorated by the algae under LDSTR. Further analysis showed that U. prolifera achieved balancing damage by means of non-photochemical quenching (NPQ), accumulation of phenolic compounds coupled with the ASA-GSH cycle involved in the antioxidant process and enhanced photorespiratory metabolism under LDSTR. This study provides new insights into the balancing damage mechanisms of U. prolifera under LDSTR, enabling the thalli to adapt to the light conditions during the long duration and distance involved in floating migration.     

Effects of Light and Nutrient Availability on Aspen: Growth, Phytochemistry, and Insect Performance

This study explored the effect of resource availability on plant phytochemical composition within the framework of carbon–nutrient balance (CNB) theory. We grew quaking aspen (Populus tremuloides) under two levels of light and three levels of nutrient availability and measured photosynthesis, productivity, and foliar chemistry [water, total nonstructural carbohydrates (TNC), condensed tannins, and phenolic glycosides]. Gypsy moths (Lymantria dispar) and forest tent caterpillars (Malacosoma disstria) were reared on foliage from each of the treatments to determine effects on insect performance. Photosynthetic rates increased under high light, but were not influenced by nutrient availability. Tree growth increased in response to both the direct and interactive effects of light and nutrient availability. Increasing light reduced foliar nitrogen, while increasing nutrient availability increased foliar nitrogen. TNC levels were elevated under high light conditions, but were not influenced by nutrient availability. Starch and condensed tannins responded to changes in resource availability in a manner consistent with CNB theory; levels were highest under conditions where tree growth was limited more than photosynthesis (i.e., high light–low nutrient availability). Concentrations of phenolic glycosides, however, were only moderately influenced by resource availability. In general, insect performance varied relatively little among treatments. Both species performed most poorly on the high light–low nutrient availability treatment. Because phenolic glycosides are the primary factor determining aspen quality for these insects, and because levels of these compounds were minimally affected by the treatments, the limited response of the insects was not surprising. Thus, the ability of CNB theory to accurately predict allocation to defense compounds depends on the response of specific allelochemicals to changes in resource availability. Moreover, whether allelochemicals serve to defend the plant depends on the response of insects to specific allelochemicals. Finally, in contrast to predictions of CNB theory, we found substantial allocation to storage and defense compounds under conditions in which growth was carbon-limited (e.g., low light), suggesting a cost to defense in terms of reduced growth.     

ATP13A2 Regulates Cellular α-Synuclein Multimerization,Membrane Association,and Externalization

ATP13A2, a late endo-/lysosomal polyamine transporter, is implicated in a variety of neurodegenerative diseases, including Parkinson’s disease and Kufor–Rakeb syndrome, an early-onset atypical form of parkinsonism. Loss-of-function mutations in ATP13A2 result in lysosomal deficiency as a consequence of impaired lysosomal export of the polyamines spermine/spermidine. Furthermore, accumulating evidence suggests the involvement of ATP13A2 in regulating the fate of α-synuclein, such as cytoplasmic accumulation and external release. However, no consensus has yet been reached on the mechanisms underlying these effects. Here, we aimed to gain more insight into how ATP13A2 is linked to α-synuclein biology in cell models with modified ATP13A2 activity. We found that loss of ATP13A2 impairs lysosomal membrane integrity and induces α-synuclein multimerization at the membrane, which is enhanced in conditions of oxidative stress or exposure to spermine. In contrast, overexpression of ATP13A2 wildtype (WT) had a protective effect on α-synuclein multimerization, which corresponded with reduced αsyn membrane association and stimulation of the ubiquitin-proteasome system. We also found that ATP13A2 promoted the secretion of α-synuclein through nanovesicles. Interestingly, the catalytically inactive ATP13A2 D508N mutant also affected polyubiquitination and externalization of α-synuclein multimers, suggesting a regulatory function independent of the ATPase and transport activity. In conclusion, our study demonstrates the impact of ATP13A2 on α-synuclein multimerization via polyamine transport dependent and independent functions.     

The Effect of Polyamines on the Photochemical Reactivity of DNA

The effects of diaminopentane (cadaverine), diaminoethane and the polyamine, spermine, on the photoreactions of 4,5′, 8-trimethylpsoralen with DNA were studied. Near ultraviolet (UV) light (360 nm) irradiation of psoralen with DNA results in the formation of psoralen monoadducts with pyrimidine bases and DNA interstrand crosslinks. The polyamines studied reduced the rate of both photoreactions to the same extent by a factor of 1.5–2.0. The magnitude of the effect increased with polyamine concentration. Effectiveness was in the order spermine > cadaverine > diaminoethane. This is also the same order for stabilization of the DNA double-helix. Under conditions of higher DNA stability (higher ionic strength), higher polyamine concentrations were required to obtain an effect which was smaller than at low ionic strength. It is concluded that the photoreactions of psoralen with pyrimidines in DNA require some distortion of the double-helix. This distortion is made more difficult in the presence of stabilizing agents like polyamines and therefore the rate of the reaction is reduced. If crosslinking of DNA by psoralen is a two-step reaction then it must be concluded that the second step does not require further distortion. Consistently with the above, polyamines also reduced the UV-induced dimerization of thymine in DNA, although to a lesser extent.     

Polyamine Profiles Of Healthy and Parasite-Infected Vaccinium Myrtillus Plants Under Nitrogen Enrichment

Addition of nitrogen (N) to the field layer of boreal forests has been shown to increase the occurrence of the parasitic fungus Valdensia heterodoxa on Vaccinium myrtillus plants. We investigated whether N addition to soil alters the levels of polyamines in V. myrtillus shoots, and discuss here whether such changes could promote the spread of the parasitic fungus on V. myrtillus. Using HPLC, we analyzed the concentrations of free and conjugated polyamines in healthy and naturally V. heterodoxa-infected V. myrtillus plants, which had received a moderate or high dose of N fertilizer, or no additional N. Fertilization with N increased the concentrations of free diamines (putrescine and diaminopropane), but had no significant effect on conjugated amines. Thus, N-induced changes in the constitutive levels of soluble conjugated amines do not seem to explain the increased parasite susceptibility of V. myrtillus under N enrichment. Generally, the concentrations of free diamines and insoluble conjugated putrescine were higher in diseased than in healthy shoots, suggesting parasite-induced accumulation of diamines. Free spermine seemed to accumulate in unfertilized, diseased plants, but in fertilized plants this induction was dampened, suggesting that N-induced alterations in spermine metabolism may promote the spread of parasites on V. myrtillus under N-enrichment.     

The Association between Spermidine/Spermine N1-Acetyltransferase (SSAT) and Human Malignancies

Spermidine/spermine N¹-acetyltransferase (SSAT) functions as a critical enzyme in maintaining the homeostasis of polyamines, including spermine, spermidine, and putrescine, in mammalian cells. SSAT is a catalytic enzyme that indirectly regulates cellular physiologies and pathways through interaction with endogenous and exogenous polyamines. Normally, SSAT exhibits only at a low cellular level, but upon tumorigenesis, the expression, protein level, and activities of SSAT are altered. The alterations induce cellular damages, including oxidative stress, cell cycle arrest, DNA dynamics, and proliferation by influencing cellular mechanisms and signaling pathways. The expression of SSAT has been reported in various studies to be altered in different cancers, and it has been correlated with tumor development and progression. Tumor grades and stages are associated with the expression levels of SSAT. SSAT can be utilized as a target for substrate binding, and excreted metabolites may be used as a novel cancer biomarker. There is also potential for SSAT to be developed as a therapeutic target. Polyamine analogs could increase SSAT expression and increase the cytotoxicity of chemotherapy to tumor cells. Drugs targeting polyamines and SSAT expression have the potential to be developed into new cancer treatments in the future.     

Non-Photochemical Quenching under Drought and Fluctuating Light

Plants grow in a variable environment in regard to soil water and light driving photochemical reactions. Light energy exceeding plant capability to use it for photochemical reactions must be dissipated by processes of non-photochemical quenching (NPQ). The aim of the study was to evaluate the impact of various components of NPQ on the response of Arabidopsis thaliana to fluctuating light and water availability. A laboratory experiment with Arabidopsis thaliana wild type (WT) and mutants npq1 and npq4 grown under optimum or reduced water availability was conducted. Dark-adapted plants were illuminated with fluctuating light (FL) of two intensities (55 and 530 μmol m⁻² s⁻¹) with each of the phases lasting for 20 s. The impact of water availability on the role of zeaxanthin and PsbS protein in NPQ induced at FL was analysed. The water deficit affected the dynamics of NPQ induced by FL. The lack of zeaxanthin or PsbS reduced plant capability to cope with FL. The synergy of both of these components was enhanced in regard to the amplitude of NPQ in the drought conditions. PsbS was shown as a component of primary importance in suiting plant response to FL under optimum and reduced water availability.     

Potential Protection Effect of ER Homeostasis of N6-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N⁶-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK–2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex^® LH–20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK–2 cells. The HK–2 cells were pretreated with HEA (10–20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF–6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.     

Defoliation-induced responses in peroxidases,phenolics, and polyamines in scots pine (Pinus sylvestris L.) needles

Effects of artificial defoliation on defensive needle chemistry in Scots pine (Pinus sylvestris L.) were evaluated with particular emphasis on peroxidases, phenolic compounds, soluble sugars, polyamines, and foliar nitrogen levels. The study was carried out on a nutrient-poor Scots pine stand with 8- to 25-year-old trees. Defoliation treatment consisted of repeated defoliation in two successive years with respective control trees. Defoliation was done before needle flushing by removing all mature needles. Guaiacol peroxidase activity increased in the needles after the first defoliation. The difference between treatments diminished towards autumn, and disappeared before the second defoliation in the next summer. After the second defoliation, the activities showed a similar trend. Apparently, peroxidases are involved in inducible chemical changes and recovery reactions that occur in the intact needles shortly after defoliation. After the second defoliation, total nitrogen concentration in the current year needles was about 20% lower, and free putrescine (a polyamine) concentration was 40% lower in the defoliated trees than in control needles. These changes indicate a loss of nitrogen due to defoliation. Specific phenolic compounds such as quercitrin, (+)-catechin, and two catechin derivatives increased in current year needles in response to defoliation. Accumulation of starch and sucrose in the current year needles of repeatedly defoliated trees may imply decreased assimilate transport. The results are indicative that changes in needle phytochemistry in response to defoliation accompany changes in needle nitrogen metabolism.     

GUN4 Affects the Circadian Clock and Seedlings Adaptation to Changing Light Conditions

The chloroplast is a key organelle for photosynthesis and perceiving environmental information. GENOME UNCOUPLED 4 (GUN4) has been shown to be required for the regulation of both chlorophyll synthesis, reactive oxygen species (ROS) homeostasis and plastid retrograde signaling. In this study, we found that growth of the gun4 mutant was significantly improved under medium strong light (200 μmol photons m⁻²s⁻¹) compared to normal light (100 μmol photons m⁻²s⁻¹), in marked contrast to wild-type (WT). Further analysis revealed that GUN4 interacts with SIGNAL RECOGNITION PARTICLE 54 KDA SUBUNIT (SRP43) and SRP54. RNA-seq analysis indicated that the expression of genes for light signaling and the circadian clock is altered in gun4 compared with (WT). qPCR analysis confirmed that the expression of the clock genes CLOCK-RELATED 1 (CCA1), LATE ELONGATION HYPOCOTYL (LHY), TIMING OF CAB EXPRESSION 1 (TOC1) and PSEUDO RESPONSE REGULATOR 7 (PRR7) is significantly changed in the gun4 and srp54 mutants under normal and medium strong light conditions. These results suggest that GUN4 may coordinate the adaptation of plants to changing light conditions by regulating the biological clock, although it is not clear whether the effect is direct or indirect.