Spermine Research Articles

Analysis of absorption-enhancing mechanisms for combinatorial use of spermine with sodium taurocholate in Caco-2 cells

Previously, we reported that the combined use of spermine (SPM) and sodium taurocholate (STC) (SPM–STC) significantly improves the oral absorption of rebamipide (BCS class IV) and pulmonary absorption of interferon-α without any harmful histopathological changes in the gastrointestinal tract and lungs, respectively. In the present study, we examined the effect of SPM–STC on the transport of fluorescein isothiocyanate-labeled dextrans (FDs) across Caco-2 cell monolayers and attempted to clarify the mechanisms underlying the transport enhancement caused by SPM–STC. SPM–STC were found to significantly enhance the transport of FDs, while the treatment with SPM–STC was not harmful, and the decrease in transepithelial electrical resistance was transient and reversible. The voltage-clamp study clearly indicated that the opening of the paracellular route could be mainly responsible for the enhanced transport of FD-4. As for the mechanisms, it was found that SPM–STC caused a significant increase in membrane fluidity, which would lead to the enhanced transport of small-molecule drugs such as rebamipide. Since SPM–STC increased intracellular Ca2+ via Ca2+ uptake through Ca2+ channels and Ca2+ release from the endoplasmic reticulum stimulated by the IP3 pathway, the subsequent possible activation of the MLCK signaling pathway would have led to the contraction of the actin–myosin ring. The rearrangement of tight junction-constituting proteins induced through the MAPK pathway has also been suggested as a possible mechanism for opening tight junctions. Claudin-4, a key protein constituting the tight junction, merged with F-actin along with the plasma membrane, was significantly decreased, which would be at least partial structural evidence for the tight-junction opening.

Effect of Storage Temperature and Time on Biogenic Amines in Canned Seafood.

Biogenic amines in canned seafood are associated with food quality and human health. In this study, a total of nine biogenic amines (histamine (HIS), phenylethylamine (PHE), tyramine (TYM), putrescine (PUT), cadaverine (CAD), tryptamine (TRY), spermine (SPM), spermidine (SPD), and octopamine (OCT)) were used as standards. The biogenic amines of five canned seafood species (canned mud carp, canned sardine, canned mantis shrimp, canned scallop, and canned oyster) were investigated every three months for 12 months at different storage temperatures (4, 10, 25, and 30 °C). The biogenic amine contents were determined by the ultrasound-assisted dispersive solid-phase extraction method combined with reversed-phase high-performance liquid chromatography-photodiode array detection (UADSPE-RPLC-PDA). These results showed a detection rate of 100, 60, and 40% for HIS, PHE, PUT, and TYM; CAD, SPM, and SPD; OCT in all the samples, respectively. The contents of histamine and tyramine exceeded the recommended maximum limits (50 and 100 mg kg−1) in the canned mud carp and canned scallop when stored at 30 °C, indicating their potential health risks (p < 0.05). This result also indicates that low temperatures could inhibit the BAs content of canned seafood during storage. Overall, storage temperature and time can be used as the primary means to monitor and control the quality and safety of canned seafood.

Chromium toxicity induced oxidative damage in two rice cultivars and its mitigation through external supplementation of brassinosteroids and spermine.

The chromium (Cr) induced phytotoxicity avowed the scientific community to develop stress mitigation strategies to restrain the Cr accumulation inside the food chain. Whereas, brassinosteroids (BRs), and spermine (SPM) are well-known growth-promoting phytohormones, which enhance the plants health, and resilient the toxic effects under stress conditions. Until now, their interactive role against Cr-mitigation is poorly known. Hence, we conducted the hydroponic experiment to perceive the behavior of seed primed with BRs, or/and SPM treatment against Cr disclosure in two different rice cultivars (CY927; sensitive, YLY689; tolerant). Our findings delineated that BRs (0.01μM), or/and SPM (0.01mM) remarkably alleviated Cr-induced phytotoxicity by improving the seed germination ratio, chlorophyll pigments, PSII system, total soluble sugar, and minimizing the MDA contents level, ROS extra generation, and electrolyte leakage through restricting the Cr accretion in roots, and shoots of both rice cultivars under Cr stress. Additionally, the BRs, or/and SPM modulated the antioxidant enzyme, and non-enzyme activities to reduce the Cr-induced cellular oxidative damage as well as maintained the ionic hemostasis in both rice cultivars, especially in YLY689. Concisely, enhanced the plants biomass and growth. Overall, our outcomes revealed that BRs and SPM interact positively to alleviate the Cr-induced damages in rice seedlings on the above-mentioned indices, and combine treatment is much more efficient than solely. Moreover, the effect of BRs, or/and SPM was more obvious in YLY689 than CY927 to hamper the oxidative stress, and boost the antioxidant capacity.

Melanoma-targeted photodynamic therapy based on hypericin-loaded multifunctional P123-spermine/folate micelles

Multifunctional P123 micelle linked covalently with spermine (SM) and folic acid (FA) was developed as a drug delivery system of hypericin (HYP). The chemical structures of the modified copolymers were confirmed by spectroscopy and spectrophotometric techniques (UV–vis, FTIR, and 1H NMR). The copolymeric micelles loading HYP were prepared by solid dispersion and characterized by UV–vis, fluorescence, dynamic light scattering (DLS), ζ potential, and transmission electron microscopy (TEM). The results provided a good level of stability for HYP-loaded P123-SM, P123-FA, and P123-SM/P123-FA in the aqueous medium. The morphology analysis showed that all copolymeric micelles are spherical. Well-defined regions of different contrast allow us to infer that SM and FA were localized on the surface of micelles, and the HYP molecules are located in the core region of micelles. The uptake potential of multifunctional P123 micelle was accessed by exposing the micellar systems loading HYP to two cell lines, B16-F10 and HaCaT. HYP-loaded P123 micelles reveal a low selectivity for melanoma cells, showing significant photodamage for HaCat cells. However, the exposition of B16-F10 cells to Hyp-loaded SM- and FA-functionalized P123 micelles under light irradiation revealed the lowest CC50 values. The interpretation of these results suggested that the combination of SM and FA on P123 micelles is the main factor in enhancing the HYP uptake by melanoma cells, consequently leading to its photoinactivation.

Seed Priming with Spermine Mitigates Chromium Stress in Rice by Modifying the Ion Homeostasis, Cellular Ultrastructure and Phytohormones Balance.

Chromium (Cr) is an important environmental constraint effecting crop productivity. Spermine (SPM) is a polyamine compound regulating plant responses to abiotic stresses. However, SPM-mediated tolerance mechanisms against Cr stress are less commonly explored in plants. Thus, current research was conducted to explore the protective mechanisms of SPM (0.01 mM) against Cr (100 µM) toxicity in two rice cultivars, CY927 (sensitive) and YLY689 (tolerant) at the seedling stage. Our results revealed that, alone, Cr exposure significantly reduced seed germination, biomass and photosynthetic related parameters, caused nutrient and hormonal imbalance, desynchronized antioxidant enzymes, and triggered oxidative damage by over-accretion of reactive oxygen species (ROS), malondialdehyde (MDA) and electrolyte leakage in both rice varieties, with greater impairments in CY927 than YLY689. However, seed priming with SPM notably improved or reversed the above-mentioned parameters, especially in YLY689. Besides, SPM stimulated the stress-responsive genes of endogenous phytohormones, especially salicylic acid (SA), as confirmed by the pronounced transcript levels of SA-related genes (OsPR1, OsPR2 and OsNPR1). Our findings specified that SPM enhanced rice tolerance against Cr toxicity via decreasing accumulation of Cr and markers of oxidative damage (H2O2, O2•− and MDA), improving antioxidant defense enzymes, photosynthetic apparatus, nutrients and phytohormone balance.

Polyamines and ethylene action blocker (STS) effectively augment longevity and postharvest attributes in isolated flowers of Digitalis purpurea L.

The present investigation focused on the study of the exogenous inclusion of anti-senescence biogenic polyamines (putrescine, spermidine and spermine) and ethylene antagonist silver thiosulphate on flower longevity and postharvest performance in excised flowers of Digitalis purpurea L. At one day before anthesis stage, isolated buds of Digitalis purpurea were transported to the laboratory in distilled water. The samples were divided into five sets with one set of flower buds (i.e., control) held in distilled water. The remaining four sets were respectively supplied with 0.5, 1 and 1.5 mM of putrescine (PUT), 0.1, 0.2 and 0.3 mM of spermidine (SPD), 0.2, 0.4 and 0.6 mM of spermine (SPM), 0.1, 0.2 and 0.3 mM of silver thiosulphate (STS). The inclusion of polyamines and STS in holding solutions enhanced the flower longevity of D. purpurea significantly compared to the control. The results indicated that the flower longevity of 14 days was recorded in 0.4 mM of spermine, followed by 13 days in 1 mM PUT, 12.5 days in 0.2 mM SPD and 12 days in 0.2 mM STS. This enhanced flower longevity corroborated with the higher values of soluble proteins, total sugars, floral diameter and membrane stability index. The improved flower longevity was also found to be positively associated with increased activities of various antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX) and reduced activity of lipoxygenase (LOX). The flowers supplemented with different treatments retained a lower phenolic content than the control. This research concluded that polyamines and STS have a profound impact on the flower longevity of Digitalis flowers. SPM was found to be a more potential polyamine in augmenting the postharvest performance in isolated flowers of D. purpurea.

Characterization of Spermidine Synthase (SPDS) Gene and RNA−Seq Based Identification of Spermidine (SPD) and Spermine (SPM) Involvement in Improving High Temperature Stress Tolerance in Gracilariopsis lemaneiformis (Rhodophyta)

Gracilariopsis lemaneiformis, an important commercial red macroalga, is facing significant impacts from global warming, which limits algal growth and yield in China. Polyamines (PAs), spermidine (SPD) and spermine (SPM), are ubiquitous polycations important for growth and environmental stress responses including high temperature (HT) tolerance. Spermidine synthase (SPDS) gene is one of the important genes in higher PA biosynthesis, which plays critical roles in HT stress response. Here, we isolated an SPDS gene from G. lemaneiformis and further analyzed its phylogenetic tree, subcellular localization, and gene expression patterns under stress conditions. Meanwhile, supplemented with SPD and SPM were used to study the effects of PAs on HT tolerance in G. lemaneiformis. It showed exogenous 0.5 mM SPD and SPM, respectively, remarkably improved the algal relative growth rate (RGR) compared to those in the CK treatment groups under HT conditions. In addition, they both significantly elevated the activities of antioxidant enzymes and significantly upregulated the expression of genes encoding antioxidant enzymes, triggered transcription factors (TFs) signaling, and improved the expression of genes encoding small heat shock proteins (sHSP20s) during HT stress. Moreover, exogenous PA also enhanced the expression of genes involved in pyruvate metabolism, ascorbate and aldarate metabolism, and nucleotide excision repair in G. lemaneiformis, which helped to maintain better energy supply, redox homeostasis, and genome integrity under HT stress. Taken together, these data provided valuable information for functional characterization of specific gene in endogenous PA synthesis and uncovered the importance of exogenous PAs in promoting algae adaptation to HT stress.

Spermine-Responsive Intracellular Self-Aggregation of Gold Nanocages for Enhanced Chemotherapy and Photothermal Therapy of Breast Cancer.

Improving the precise accumulation and retention of nanomedicines in tumor cells is one of the keys to effective therapy of tumors. Herein, supramolecular peptides capped Au nanocages (AuNCs) that may self-aggregate into micron-sized clusters intracellularly in response to spermine (SPM), leading to specific accumulation and retention of AuNCs in SPM-overexpressed tumor cells, are developed. In this design, polydopamine (PDA) is in situ coated on the surface of AuNCs with doxorubicin (DOX) encapsulated. A small peptide, Phe-Phe-Val-Leu-Lys (FFVLK), is conjugated with PDA via esterification, and cucurbit[7]uril (CB[7]) is threaded onto the N-terminal Phe via host-guest interactions. Once the supramolecular peptide (CB[7]-FFVLK) capped AuNCs are internalized in SPM-overexpressed breast cancer cells, CB[7] can be competitively removed from FFVLK by SPM, due to the much higher binding affinity between CB[7] and SPM than that between CB[7] and Phe, leading to exposure of free FFVLK, which can subsequently self-assemble and induce the aggregation of AuNCs to micron-sized clusters, resulting in the significantly enhanced accumulation and retention of DOX-loaded AuNCs in tumor cells. Under NIR laser irradiation, the enhanced photothermal conversion of AuNCs aggregates, together with photothermia-induced release of DOX leads to synergistic photothermal therapy and chemotherapy against breast cancer.

Developmental and phytochemical changes in pot marigold (Calendula officinalis L.) using exogenous application of polyamines

Polyamines (PAs) are natural active compounds having more than two amino groups that play important roles in many physiological and developmental processes in plants. The purpose of this research was to see how foliar polyamine spray affected growth and photosynthetic indices, as well as secondary metabolites and antioxidant activity of the aqueous and methanolic extracts of pot marigold (Calendula officinalis L.). The experiment lasted for three months and was arranged in a randomized complete design with four replications. Three separate concentrations (0.5, 1 and 2.5 mM) of spermine (SPM), spermidine (SPD), and putrescine (PUT) were sprayed at four/five fully expanded leaf stage and some physiochemical attributes were evaluated. The treatments caused a significant increase in morphological and photosynthetic parameters and total oil. There were also significant variations in total phenolic and flavonoid content. Compared to other polyamines, 1 mM SPD foliar spraying showed the greatest effect. Furthermore, the highest antioxidant capacity (DPPH* scavenging assay, ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC) and β-carotene bleaching activity) was observed in the 1 mM SPD treatment. The results showed that the calendula essential oils (EOs) were rich in sesquiterpenes hydrocarbons (55.92–95.94%), with c-Cadinene and d-Cadinene as the major sesquiterpenes in the EOs. Also, the flowers were rich sources of carotenoids (lutein, flavoxanthin and luteoxanthin) following polyamines application. Hence, it can be inferred that polyamines specially spermidine would find a wide range of application in pharmaceutical industries due to its impact on antioxidant properties of phenolic and flavonoid compounds.

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host-guest interaction for drug delivery.

A new water-soluble hexacarboxylated tribenzotriquinacene derivative (TBTQ-CB6) was synthesized and used as a supramolecular drug carrier to load the model anticancer drugs dimethyl viologen (MV) and doxorubicin (DOX) via host–guest interactions. The drugs could be effectively released by spermine (SM), a molecule overexpressed in cancer cells, through host–guest competitive substitution since TBTQ-CB6 has a stronger binding affinity toward SM than MV and DOX. The host–guest interactions of the complexes of TBTQ-CB6 with MV, DOX and SM were investigated by NMR spectroscopy and fluorescence spectroscopy. The association stoichiometry of the complexes of TBTQ-CB6 with MV, DOX, and SM was found to be 1:1 with association constants of Ka = (7.67 ± 0.34) × 104 M−1, Ka = (6.81 ± 0.33) × 104 M−1, and Ka = (5.09 ± 0.98) × 105 M−1, respectively. The competitive substitution process was visualized by NMR titration. This novel TBTQ-based host–guest drug delivery system may have potential use in supramolecular chemotherapy.

Novel gluconate stabilized gold nanoparticles as a colorimetric sensor for quantitative evaluation of spermine

In the fields of biology and pharmacy, water dispersible gold nanoparticles (AuNPs) with bio-friendly capping agents are always in demand. Gluconate is a substance that is compatible with biological systems. Gluconate stabilized AuNPs (abbrv.: Glu-AuNPs) were synthesized in water and characterized utilizing UV-Vis spectroscopy, DLS, TEM, and Raman spectroscopy tools, as well as a DFT computing investigation. The Glu-AuNPs are extremely stable in the pH range of 4–10 and exhibit SPR band maximum at 518 nm. According to TEM and DLS investigation, the particle sizes are 7.03 ± 2 nm and 14 nm, respectively. They have an FCC crystalline structure. The Raman and DFT computation studies reveal that the gluconate ions adsorbed onto the surface of AuNPs and provided much needed stability of the particles against agglomeration. The computed binding energy of Glu-O(COO) to Au3 cluster is − 5.22 eV, which is quite high. The particles have been ascertained as colorimetric and UV-Vis spectrophotometric nanosensor for spermine (SM), a biomarker for cancer diagnosis. The SM was quantified by monitoring changes in the feature of the SPR band maximum of Glu-AuNPs as a result of its aggregation. The LoD value is 0.2511 μM. As evidenced by the computed Kasso value of 2.183 × 106 M−1, the SM---AuNPs interactions are quite strong. The nanosensor exhibits excellent recovery results against real samples.

Involvement of Polyamines From Cardiac Mast Cells in Myocardial Remodeling Induced by Pressure Overload Through Mitochondrial Permeability Transition Pore Opening.

ObjectivePolyamines mainly contain spermine (SPM), spermidine (SPD), and putrescine (PUT). Many research results suggest that polyamines participate in cell proliferation, differentiation, and the regulation of gene expression, and have a close relationship with the occurrence and development of many diseases. However, the role and possible mechanisms of action of polyamines from cardiac mast cells in myocardial remodeling induced by pressure overload remain to be elucidated.MethodsPressure overload was induced by abdominal aortic constriction (AAC). Toluidine blue staining was used to visualize mast cells in cardiac tissue. The polyamine content of cardiac tissue was analyzed using high-performance liquid chromatography. Opening of the mitochondrial permeability transition pore (MPTP) was determined by the Ca2+-induced swelling of isolated cardiac mitochondria, measured as a reduction in A520.ResultsCompared with sham rats, the cardiac mast cell density, the polyamine content (PUT, SPB, and SPM), and myocardial MPTP opening in rats with AAC were significantly increased (P < 0.05), and were accompanied by increased myocardial fibrosis and heart weight/body weight ratio. Intraperitoneal injection of polyamines mimicked these results, and these effects were reversed by cromolyn sodium, a mast cell stabilizer (P < 0.05). Myocardial MPTP opening increased in rats with AAC (P < 0.05), and the three polyamines also increased myocardial MPTP opening (P < 0.05).ConclusionMast cell-derived polyamines are involved in pressure overload-induced myocardial remodeling by increasing opening of the MPTP.

Transcriptomics Coupled to Proteomics Reveals Novel Targets for the Protective Role of Spermine in Diabetic Cardiomyopathy.

Background Diabetic cardiomyopathy (DbCM) is the main complication and the cause of high mortality of diabetes. Exploring the transcriptomics and proteomics of DbCM is of great significance for understanding the biology of the disease and for guiding new therapeutic targets for the potential therapeutic effect of spermine (SPM). Methods and Results By using a mouse DbCM model, we analyzed the overall transcriptome and proteome of the myocardium, before/after treatment with SPM. The general state and cardiac structure and function changes of each group were also compared. Diabetes induced an increased blood glucose and serum triglyceride content, a decreased body weight, serum insulin level, and cardiac function-related indexes, accompanied by disrupted myocardial tissue morphology and ultrastructure damage. Using RNA sequencing (RNA-seq), we identified thousands of differentially expressed genes (DEGs) in DbCM with or without SPM treatment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis demonstrated that the DEGs were significantly enriched in lipid metabolism and amino acid metabolism pathways. Specifically, quantitative real-time PCR (qRT-PCR) confirmed that SPM protected DbCM by reversing the expressions of lipid metabolism and amino acid metabolism-related genes, including Alox15, Gm13033, pla2g12a, Ptges, Pnpla2, and Acot1. To further reveal the pathogenesis of DbCM, we used proteome-based data-independent acquisition (DIA) and identified 139 differentially expressed proteins (DEPs) with 67 being upregulated and 72 being downregulated in DbCM. Venn intersection analysis showed 37 coexpressed genes and proteins in DbCM, including 29 upregulation and 8 downregulation in DbCM. In the protein-protein interaction (PPI) network constructed by the STRING database, the metabolism-related coexpressed genes and proteins, such as Acot2, Ephx2, Cyp1a1, Comt, Acox1, Hadhb, Hmgcs2, Acot1, Inmt, and Cat, can interact with the identified DEGs and DEPs. Conclusion The biomarkers and canonical pathways identified in this study may hold the key to understand the mechanisms of DbCM pathobiology and provide new targets for the therapeutic effect of SPM against DbCM by targeting lipid and amino acid metabolism pathways.

Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation

Multiple sclerosis (MS) is a chronic neuroinflammatory disease which causes demyelination, axonal damage and even disability. Th1 and Th17 cells, more precisely, the IFNγ/IL17a double producing CD4+ T cells, have been known to play critical roles in the pathogenesis of MS and EAE, a mouse model of MS. Polyamines not only regulate the immune system, but also are essential for the normal function of the central nervous system (CNS). In this study, we demonstrate that the supplementation of spermine (SPM), a biogenic polyamine, significantly suppresses EAE progression in both preventative and therapeutic ways. Further study suggests that spermine significantly reduces IFNγ+/IL17a-, IFNγ-/IL17a+ and IFNγ+/IL17a+ cells in periphery, and thus reducing the infiltration of these pathogenic cells into the CNS. In vitro, spermine has been shown to suppress the activation and proliferation of CD4+ T cells and also significantly impede the polarization of T effector cells in a dose-dependent manner, accompanied by the inhibition of ERK phosphorylation. Consistently, a number of MEK/ERK inhibitors (including PD0325901, FR180204 and selumetinib) have been found to mimic the effects of spermine in inhibiting CD4+ T cell activation and T effector cell differentiation. Collectively, spermine alleviates EAE progression by inhibiting CD4+ T cells activation and T effector cell differentiation in a MAPK/ERK–dependent manner, suggesting this pathway might be a target to develop effective therapies for MS.

Determination of spermine and spermidine in meat with a ratiometric fluorescence nanoprobe and a combinational logic gate

A ratiometric fluorescent nanoprobe is developed with a wide color variation for visual determination of spermine (SP) and spermidine (SD) in meat samples. The green emission provided from the combination of yellow emissive quantum dots and blue emissive carbon dots turns into pink when SP or SD are present. The results show that the developed sensor has good linearity in the range of 0.5–10 and 0.5–80 µM for SP and SD and suitable detection limits were achieved including 0.2 and 2.1 µM for SP and SD. The probe was highly selective in the presence of amino acids and other biogenic amines. RGB indices were extracted to build a combinational logic gate for visual and simultaneous detection of SP and SD. The dual functional logic gate was easy to design and convenient to operate. Finally, a portable sensor was fabricated for visual, rapid and on-site assessment of meat freshness.

Spermine Regulates Immune and Signal Transduction Dysfunction in Diabetic Cardiomyopathy.

BackgroundDiabetic cardiomyopathy (DCM) is a specific form of cardiomyopathy that is independent of coronary artery disease and hypertension. Exploring the transcriptomics of DCM is of great significance for understanding the biology of the disease and for guiding new therapeutic targets for the potential therapeutic effect of spermine (SPM).Methods and ResultsBy using a mouse DCM model, we analyzed the transcriptome of the myocardium, before/after treatment with SPM. Using RNA sequencing (RNA-seq), we identified 1,318 differentially expressed genes (DEGs), with 636 being upregulated and 682 being downregulated in DCM compared to control check (CK). We then identified 1,393 DEGs, with 887 being upregulated and 506 being downregulated in SPM compared to DCM. Kyoto Encyclopedia of Genes And Genomes (KEGG) analysis demonstrated that the DEGs were significantly enriched in the immune system and signal transduction-related pathways. UpSet Venn analysis showed that 174 DEGs in DCM could be reversed by SPM, with 45 candidates related to immune system and related signal transduction pathways. Trend analysis demonstrated the dynamic changes in gene levels in DCM and SPM treatment, shown as 49 immune and signal transduction-related candidates were significantly enriched in some classical pathways, such as complement and coagulation cascades and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway. To further reveal the protective mechanism of SPM to DCM, we predicted 14 overlapped transcription factors (TFs) and their co-factors involved in gene transcription regulation and showed gene interaction with Cytoscape.ConclusionThe biomarkers and canonical pathways identified in this study may hold the key to understanding the mechanisms of DCM pathobiology and providing new targets for the therapeutic effect of SPM against DCM by targeting abnormal immune response and signal transduction.

Critical Role of Astrocytic Polyamine and GABA Metabolism in Epileptogenesis.

Accumulating evidence indicate that astrocytes are essential players of the excitatory and inhibitory signaling during normal and epileptiform activity via uptake and release of gliotransmitters, ions, and other substances. Polyamines can be regarded as gliotransmitters since they are almost exclusively stored in astrocytes and can be released by various mechanisms. The polyamine putrescine (PUT) is utilized to synthesize GABA, which can also be released from astrocytes and provide tonic inhibition on neurons. The polyamine spermine (SPM), synthesized form PUT through spermidine (SPD), is known to unblock astrocytic Cx43 gap junction channels and therefore facilitate astrocytic synchronization. In addition, SPM released from astrocytes may also modulate neuronal NMDA, AMPA, and kainate receptors. As a consequence, astrocytic polyamines possess the capability to significantly modulate epileptiform activity. In this study, we investigated different steps in polyamine metabolism and coupled GABA release to assess their potential to control seizure generation and maintenance in two different epilepsy models: the low-[Mg2+] model of temporal lobe epilepsy in vitro and in the WAG/Rij rat model of absence epilepsy in vivo. We show that SPM is a gliotransmitter that is released from astrocytes and significantly contributes to network excitation. Importantly, we found that inhibition of SPD synthesis completely prevented seizure generation in WAG/Rij rats. We hypothesize that this antiepileptic effect is attributed to the subsequent enhancement of PUT to GABA conversion in astrocytes, leading to GABA release through GAT-2/3 transporters. This interpretation is supported by the observation that antiepileptic potential of the Food and Drug Administration (FDA)-approved drug levetiracetam can be diminished by specifically blocking astrocytic GAT-2/3 with SNAP-5114, suggesting that levetiracetam exerts its effect by increasing surface expression of GAT-2/3. Our findings conclusively suggest that the major pathway through which astrocytic polyamines contribute to epileptiform activity is the production of GABA. Modulation of astrocytic polyamine levels, therefore, may serve for a more effective antiepileptic drug development in the future.

A combination of a graphene quantum dots-cationic red dye donor-acceptor pair and cucurbit[7]uril as a supramolecular sensor for ultrasensitive detection of cancer biomarkers spermine and spermidine.

In a unique approach, the combination of a donor-acceptor pair of hydroxy graphene quantum dots (GQDs-OH) and a red-emissive donor-two-acceptor (D-2-A) type dye with pyridinium units (BPBP) and the well-known host cucurbit[7]uril (CB[7]) has been exploited as a supramolecular sensing assembly for the detection of cancer biomarkers spermine and spermidine in aqueous media at the sub-ppb level based on the affinity-driven exchange of guests from the CB[7] portal. In the binary conjugate, green fluorescent GQDs-OH transfers energy to trigger the emission of the dye BPBP and itself remains in the turn-off state. CB[7] withdraws the dye from the surface of GQDs-OH by strong host-guest interactions with its portal, making GQDs-OH fluoresce again to produce a ratiometric response. In the presence of spermine (SP) or spermidine (SPD), their strong affinity with CB[7] forces the ejection of the fluorophore to settle on the GQDs-OH surface, and the strong green emission of GQDs-OH turns off to device a supramolecular sensor for the detection of SP/SPD. The DFT studies revealed interesting excited-state charge-transfer conjugate formation between BPBP and GQDs leading to turn-on emission of the dye, and further supported the stronger binding modes of BPBP-CB[7], indicating the retrieval of the emission of GQDs. The assembly-disassembly based sensing mechanism was also established by Job's plot analysis, particle size analysis, zeta potential, time-resolved spectroscopy, ITC studies, microscopic studies, etc. The supramolecular sensing assembly is highly selective to SP and SPD, and showed nominal interference from other biogenic amines, amino acids, various metal ions, and anions. The limits of detection (LODs) were 0.1 ppb and 0.9 ppb for spermine and spermidine, respectively. The potential for the real-world application of this sensing assembly was demonstrated by spiking SP and SPD in human urine and blood serum with a high %recovery.

Exogenous polyamine treatment preserves postharvest quality, antioxidant compounds and reduces lipid peroxidation in black plum fruit

Black plum (Syzygium cumini L. Skeels) is a tropical and sub-tropical fruit having several medicinal properties, especially in curing diabetes. Due to non-climacteric nature, the fruit is harvested at ripe stage. However, presence of thin skin and rapid softening make the fruit highly susceptible to moisture loss and microbial attack, which drastically reduce its shelf life. Black plum, due to its high perishability cannot be stored more than 2 – 3 days at ambient conditions. In the present study, the effect of pre-storage polyamines treatment on quality and storability of black plum fruit was investigated. Ripe fruits were treated with putrescine (PUT) and spermine (SPM) each at 0.5 mM and 1.0 mM concentration by immersion method while, control fruit were treated with distilled water. The fruit were stored at ambient conditions (27 ± 3 °C, 85 ± 5% RH) for 6 days. Results revealed that 1.0 mM PUT treatment was most effective in minimizing weight loss and spoilage of about 1.5-fold compared to control. The treated fruits also retained higher anthocyanins and minimized lipid peroxidation than control. The loss of bioactive compounds like total phenolics, flavonoids, ascorbic acid and antioxidant capacity also minimized in response to polyamine treatments. The soluble solids content retained higher in 1.0 mM PUT-treated fruits but, polyamine treatments did not affect acid content. The findings of the study can be beneficially exploited in extending storability, long distant marketing and reducing postharvest loss of black plum fruit.

Polyamines accentuate vase life by augmenting antioxidant system in cut spikes of Consolida ajacis (L.) Schur.

Abstract Postharvest senescence is one of the crucial challenges limiting the marketability of cut flowers. Pertinently, recent investigations implicate extensive role of polyamines in regulation of flower senescence. The present study was envisaged to test the efficacy of poylamines in preserving the postharvest quality of Consolida ajacis (C. ajacis) cut spikes. The cut spikes of C. ajacis were subjected to various treatments of polyamines viz, 4 mM Spermine (SPM), 6mM Putrescine (PUT) and 6 mM Spermidine (SPD). A separate set of spikes held in distilled water represented the control. Our results authenticate a significant improvement in vase life of cut spikes of C. ajacis as compared to control. The increment in vase life was commensurate with the higher concentration of sugars, proteins and phenols in the tepal tissues. Polyamines amplified the activity of various antioxidant enzymes viz, superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) to overcome the deleterious effects of reactive oxygen species (ROS). The membrane outflow of tepal tissues was profoundly reduced due to attenuated lipoxygenase (LOX) activity. These findings reveal conspicuous role of polyamines particularly SPM in modulation of flower senescence in cut spikes of C. ajacis.