RESUMO
Previous studies have already highlighted the correlation between Sporisorium scitamineum pathogenicity and sugarcane polyamine accumulation. It was shown that high infectivity correlates with an increase in the amount of spermidine, spermine and cadaverine conjugated to phenols in the sensitive cultivars whereas resistant plants mainly produce free putrescine. However, these previous studies did not clarify the role of these polyamides in the disorders caused to the plant. Therefore, the purpose of this research is to clarify the effect of polyamines on the development of smut disease. In this paper, commercial polyamines were firstly assayed on smut teliospores germination. Secondly, effects were correlated to changes in endogenous polyamines after contact with defense sugarcane glycoproteins. Low concentrations of spermidine significantly activated teliospore germination, while putrescine had no activating effect on germination. Interestingly, it was observed that the diamine caused nuclear decondensation and breakage of the teliospore cell wall whereas the treatment of teliospores with spermidine did not induce nuclear decondensation or cell wall breakdown. Moreover, the number of polymerized microtubules increased in the presence of 7.5 mM spermidine but it decreased with putrescine which indicates that polyamines effects on Sporisorium scitamineum teliospore germination could be mediated through microtubules interaction. An increased production of polyamines in smut teliospores has been related to sugarcane resistance to the disease. Teliospores incubation with high molecular mass glycoproteins (HMMG) from the uninoculated resistant variety of sugarcane, Mayari 55-14, caused an increase of the insoluble fraction of putrescine, spermidine and spermine inside the teliospore cells. Moreover, the level of the soluble fraction of spermidine (S fraction) increased inside teliospores and the excess was released to the medium. The HMMG glycoproteins purified from Mayarí 55-14 plants previously inoculated with the pathogen significantly increased the levels of both retained and secreted soluble putrescine and spermidine. Polyamines levels did not increase in teliospores after incubation with HMMG produced by non resistant variety Barbados 42231 which could be related to the incapacity of these plants to defend themselves against smut disease. Thus, a hypothesis about the role of polyamines in sugarcane-smut interaction is explained.
Assuntos
Poliaminas Biogênicas/metabolismo , Glicoproteínas/metabolismo , Imunidade Vegetal , Saccharum/microbiologia , Esporos Fúngicos/metabolismo , Ustilaginales/metabolismo , Poliaminas Biogênicas/fisiologia , Glicoproteínas/fisiologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Putrescina/metabolismo , Putrescina/fisiologia , Saccharum/metabolismo , Espermidina/metabolismo , Espermidina/fisiologia , Espermina/metabolismo , Espermina/fisiologia , Ustilaginales/fisiologiaRESUMO
AIMS: Ageing is associated with cardiovascular disease and reduced cardiac function. This cardiac functional decline is accompanied by cardiac remodeling and alterations in cardiomyocyte composition. Recently, it was shown that the natural polyamine spermidine preserves cardiac function and cardiomyocyte composition in old mice. As cardiac function critically relies on blood supply, we tested whether spermidine has also beneficial effects on ageing-associated changes of the myocardial microcirculation. METHODS: Using transmission electron microscopy, the left ventricular capillaries of young (4-months old) and aged (24-months old) C57BL/6J male mice were investigated by stereology. Aged mice were subdivided into an untreated group and a group that was fed spermidine late in life for 6â¯months. Specifically, total volume, surface area and length of capillaries as well as endothelial thickness were estimated. Additionally, the total length of precapillary arterioles was assessed. The protein level of VEGF-A was measured using Western blot. RESULTS: Ageing was associated with whole heart and left ventricular hypertrophy. All total capillary-related values (including volume, surface area and length) were significantly higher in 24-month-old mice compared with 4-month-old mice. Moreover, VEGF-A expression was significantly enhanced in aged mice. The mean thickness of the endothelium was not different, but the mean area of myocardium supplied by capillaries was smaller in old mice. Spermidine treatment had no significant effect on the ageing-associated structural changes or VEGF-A expression. CONCLUSIONS: In conclusion, in the left ventricles of aged mice the growth of capillaries and arterioles supplying cardiomyocytes were in proportion to whole organ hypertrophy. Spermidine had no effect on quantitative characteristics of capillaries or arterioles, suggesting that the beneficial effects of spermidine on the ageing heart do not depend on the quantitative structural characteristics of the microcirculation which does not exclude potential functional differences between the groups.
Assuntos
Envelhecimento/patologia , Envelhecimento/fisiologia , Cardiotônicos/administração & dosagem , Miocárdio/patologia , Espermidina/administração & dosagem , Espermidina/fisiologia , Animais , Circulação Coronária/efeitos dos fármacos , Circulação Coronária/fisiologia , Hipertrofia Ventricular Esquerda/patologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microcirculação/efeitos dos fármacos , Microcirculação/fisiologia , Microvasos/efeitos dos fármacos , Microvasos/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Spermidine is a natural polyamine that stimulates cytoprotective macroautophagy/autophagy. External supplementation of spermidine extends lifespan and health span across species, including in yeast, nematodes, flies and mice. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentrations and age-related deterioration has been suggested. Recent epidemiological data support this notion, showing that an increased uptake of this polyamine with spermidine-rich food diminishes overall mortality associated with cardiovascular diseases and cancer. Here, we discuss nutritional and other possible routes to counteract the age-mediated decline of spermidine levels.
Assuntos
Envelhecimento/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Espermidina/farmacologia , Espermidina/fisiologia , Envelhecimento/fisiologia , Animais , Autofagia/fisiologia , Humanos , Camundongos , Nematoides , Regulação para Cima/efeitos dos fármacos , Vitaminas/farmacologia , Vitaminas/fisiologia , LevedurasRESUMO
KEY MESSAGE: The mechanism of exogenous Spd-induced Ca(NO3)2 stress tolerance in cucumber was studied by proteomics and physiological analyses. Protein-protein interaction network revealed 13 key proteins involved in Spd-induced Ca(NO3)2 stress resistance. Ca(NO3)2 stress is one of the major reasons for secondary salinization that limits cucumber plant development in greenhouse. The conferred protective role of exogenous Spd on cucumber in response to Ca(NO3)2 stress cues involves changes at the cellular and physiological levels. To investigate the molecular foundation of exogenous Spd in Ca(NO3)2 stress tolerance, a proteomic approach was performed in our work. After a 9 days period of Ca(NO3)2 stress and/or exogenous Spd, 71 differential protein spots were confidently identified. The resulting proteins were enriched in seven different categories of biological processes, including protein metabolism, carbohydrate and energy metabolism, ROS homeostasis and stress defense, cell wall related, transcription, others and unknown. Protein metabolism (31.2%), carbohydrate and energy metabolism (15.6%), ROS homeostasis and stress defense (32.5%) were the three largest functional categories in cucumber root and most of them were significantly increased by exogenous Spd. The Spd-responsive protein interaction network revealed 13 key proteins, whose accumulation changes could be critical for Spd-induced resistance; all 13 proteins were upregulated by Spd at transcriptional and protein levels in response to Ca(NO3)2 stress. Furthermore, accumulation of antioxidant enzymes, non-enzymatic antioxidant and polyamines, along with reduction of H2O2 and MDA, were detected after exogenous Spd application during Ca(NO3)2 stress. The results of these proteomic and physiological analyses in cucumber root may facilitate a better understanding of the underlying mechanism of Ca(NO3)2 stress tolerance mediated by exogenous Spd.
Assuntos
Compostos de Cálcio/metabolismo , Cucumis sativus/fisiologia , Nitratos/metabolismo , Espermidina/fisiologia , Proteínas de Plantas/metabolismo , Raízes de Plantas/fisiologia , Proteômica , Plântula/fisiologia , Estresse FisiológicoRESUMO
Changes in the levels of polyamines are correlated with the activation or repression of developmental response pathways, but the role of polyamine transporters in the regulation of polyamine homeostasis and thus indirectly gene expression, has not been previously addressed. Here we show that the A. thaliana and rice transporters AtPUT5 and OsPUT1 were localized to the ER, while the AtPUT2, AtPUT3, and OsPUT3 were localized to the chloroplast by transient expression in N. benthamiana. A. thaliana plants that were transformed with OsPUT1 under the control the PUT5 promoter were delayed in flowering by 16days. In contrast, put5 mutants flowered four days earlier than WT plants. The delay of flowering was associated with significantly higher levels of spermidine and spermidine conjugates in the leaves prior to flowering. A similar delay in flowering was also noted in transgenic lines with constitutive expression of either OsPUT1 or OsPUT3. All three transgenic lines had larger rosette leaves, thicker flowering stems, and produced more siliques than wild type plants. In contrast, put5 plants had smaller leaves, thinner flowering stems, and produced fewer siliques. Constitutive expression of PUTs was also associated with an extreme delay in both plant senescence and maturation rate of siliques. These experiments provide the first genetic evidence of polyamine transport in the timing of flowering, and indicate the importance of polyamine transporters in the regulation of flowering and senescence pathways.
Assuntos
Flores/crescimento & desenvolvimento , Espermidina/fisiologia , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Transporte Biológico/fisiologia , Proteínas de Transporte/fisiologia , Cloroplastos/metabolismo , Cloroplastos/fisiologia , Flores/fisiologia , Regulação da Expressão Gênica de Plantas/fisiologia , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Oryza/fisiologia , TranscriptomaRESUMO
The ATM (ataxia telangiectasia mutated) protein has recently been proposed to play critical roles in the response to mitochondrial dysfunction by initiating mitophagy. Here, we have used ATM-proficient GM00637 cells and ATM-deficient GM05849 cells to investigate the mitophagic effect of spermidine and to elucidate the role of ATM in spermdine-induced mitophagy. Our results indicate that spermidine induces mitophagy by eliciting mitochondrial depolarization, which triggers the formation of mitophagosomes and mitolysosomes, thereby promoting the accumulation of PINK1 and translocation of Parkin to damaged mitochondria, finally leading to the decreased mitochondrial mass in GM00637 cells. However, in GM05849 cells or GM00637 cells pretreated with the ATM kinase inhibitor KU55933, the expression of full-length PINK1 and the translocation of Parkin are blocked, and the colocalization of Parkin with either LC3 or PINK1 is disrupted. These results suggest that ATM drives the initiation of the mitophagic cascade. Our study demonstrates that spermidine induces mitophagy through ATM-dependent activation of the PINK1/Parkin pathway. These findings underscore the importance of a mitophagy regulatory network of ATM and PINK1/Parkin and elucidate a novel mechanism by which ATM influences spermidine-induced mitophagy.
Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/fisiologia , Mitofagia/fisiologia , Proteínas Quinases/metabolismo , Espermidina/fisiologia , Ubiquitina-Proteína Ligases/metabolismo , Linhagem Celular , Fibroblastos/metabolismo , Humanos , Potencial da Membrana Mitocondrial/fisiologiaRESUMO
Polyamines are small, ubiquitous, nitrogenous compounds that scavenge reactive oxygen species and stabilize the structure and function of the photosynthetic apparatus in response to abiotic stresses. Molecular details underlying polyamine-mediated photoprotective mechanisms are not completely resolved. This study investigated the role of spermidine (Spd) in the structure and function of the photosynthetic apparatus. Tomato seedlings were subjected to salinity-alkalinity stress with and without foliar application of Spd, and photosynthetic and morphological parameters were analyzed. Leaf dry weight and net photosynthetic rate were reduced by salinity-alkalinity stress. Salinity-alkalinity stress reduced photochemical quenching parameters, including maximum photochemistry efficiency of photosystem II, quantum yield of linear electron flux, and coefficient of photochemical quenching (qP). Salinity-alkalinity stress elevated nonphotochemical quenching parameters, including the de-epoxidation state of the xanthophyll cycle and nonphotochemical quenching (NPQ). Microscopic analysis revealed that salinity-alkalinity stress disrupted the internal lamellar system of granal and stromal thylakoids. Exogenous Spd alleviated the stress-induced reduction of leaf dry weight, net photosynthetic rate, and qP parameters. The NPQ parameters increased by salinity-alkalinity stress were also alleviated by Spd. Seedlings treated with exogenous Spd had higher zeaxanthin (Z) contents than those without Spd under salinity-alkalinity stress. The chloroplast ultrastructure had a more ordered arrangement in seedlings treated with exogenous Spd than in those without Spd under salinity-alkalinity stress. These results indicate that exogenous Spd can alleviate the growth inhibition and thylakoid membrane photodamage caused by salinity-alkalinity stress. The Spd-induced accumulation of Z also may have an important role in stabilizing the photosynthetic apparatus.
Assuntos
Salinidade , Plântula/fisiologia , Solanum lycopersicum/fisiologia , Espermidina/fisiologia , Clorofila/química , Cloroplastos/ultraestrutura , Microscopia Eletrônica de Transmissão , Fotossíntese , Complexo de Proteína do Fotossistema II/fisiologia , Pigmentação , Espécies Reativas de Oxigênio/química , Sais/química , Tilacoides/ultraestrutura , Xantofilas/químicaRESUMO
Formation of Bacillus subtilis biofilms, consisting of cells encapsulated within an extracellular matrix of exopolysaccharide and protein, requires the polyamine spermidine. A recent study reported that (1) related polyamine norspermidine is synthesized by B. subtilis using the equivalent of the Vibrio cholerae biosynthetic pathway, (2) exogenous norspermidine at 25 µM prevents B. subtilis biofilm formation, (3) endogenous norspermidine is present in biofilms at 50-80 µM, and (4) norspermidine prevents biofilm formation by condensing biofilm exopolysaccharide. In contrast, we find that, at concentrations up to 200 µM, exogenous norspermidine promotes biofilm formation. We find that norspermidine is absent in wild-type B. subtilis biofilms at all stages, and higher concentrations of exogenous norspermidine eventually inhibit planktonic growth and biofilm formation in an exopolysaccharide-independent manner. Moreover, orthologs of the V. cholerae norspermidine biosynthetic pathway are absent from B. subtilis, confirming that norspermidine is not physiologically relevant to biofilm function in this species.
Assuntos
Bacillus subtilis/fisiologia , Biofilmes/crescimento & desenvolvimento , Espermidina/análogos & derivados , Sequência de Aminoácidos , Bacillus subtilis/crescimento & desenvolvimento , Dados de Sequência Molecular , Plâncton/crescimento & desenvolvimento , Alinhamento de Sequência , Espermidina/biossíntese , Espermidina/metabolismo , Espermidina/fisiologia , Vibrio cholerae/fisiologia , Ácido gama-Aminobutírico/metabolismoRESUMO
Aliphatic polyamines are a family of polycationic molecules derived from decarboxylation of the amino acid ornithine that classically comprise three molecules: putrescine, spermidine and spermine. In-cell polyamine homeostasis is tightly controlled at key steps of cell metabolism. Polyamines are involved in an array of cellular functions from DNA stabilization, and regulation of gene expression to ion channel function and, particularly, cell proliferation. As such, aliphatic polyamines play an essential role in rapidly dividing cells such as in the immune system and digestive tract. Because of their role in cell proliferation, polyamines are also involved in carcinogenesis, prompting intensive research into polyamine metabolism as a target in cancer therapy. More recently, another aliphatic polyamine, agmatine, the decarboxylated derivative of arginine, has been identified as a neurotransmitter in mammals, and investigations have focused on its effects in the CNS, notably as a neuroprotector in brain injury.
Assuntos
Putrescina/fisiologia , Espermidina/fisiologia , Espermina/fisiologia , Agmatina/metabolismo , Animais , Modelos Animais de Doenças , Humanos , Neoplasias/patologia , Ornitina/fisiologiaRESUMO
Spermidine is a naturally occurring polyamine involved in multiple biological processes, including DNA metabolism, autophagy and aging. Like other polyamines, spermidine is also indispensable for successful reproduction at several stages. However, a direct influence on the actual fertilization process, i.e., the fusion of an oocyte with a spermatocyte, remains uncertain. To explore this possibility, we established the mating process in the yeast Saccharomyces cerevisiae as a model for fertilization in higher eukaryotes. During human fertilization, the sperm capacitates and the acrosome reaction is necessary for penetration of the oocyte. Similarly, sexually active yeasts form a protrusion called "shmoo" as a prerequisite for mating. In this study, we demonstrate that pheromone-induced shmoo formation requires spermidine. In addition, we show that spermidine is essential for mating in yeast as well as for egg fertilization in the nematode Caenorhabditis elegans. In both cases, this occurs independently from autophagy. In synthesis, we identify spermidine as an important mating component in unicellular and multicellular model organisms, supporting an unprecedented evolutionary conservation of the mechanisms governing fertilization-related cellular fusion.
Assuntos
Extensões da Superfície Celular/fisiologia , Fertilização/fisiologia , Feromônios/farmacologia , Espermidina/fisiologia , Animais , Autofagia/fisiologia , Caenorhabditis elegans , Extensões da Superfície Celular/efeitos dos fármacos , Cromatografia Líquida , Microscopia de Fluorescência , Poliaminas/metabolismo , Reprodução/fisiologia , Saccharomyces cerevisiae , Espectrometria de Massas em TandemRESUMO
Spermine (SPM) and spermidine, endogenous polyamines with the ability to modulate various ion channels and receptors in the brain, exert neuroprotective, antidepressant, antioxidant, and other effects in vivo such as increasing longevity. These polyamines are preferably accumulated in astrocytes, and we hypothesized that SPM increases glial intercellular communication by interacting with glial gap junctions. The results obtained in situ, using Lucifer yellow propagation in the astrocytic syncitium of 21-25-day-old rat CA1 hippocampal slices, showed reduced coupling when astrocytes were dialyzed with standard intracellular solutions without SPM. However, there was a robust increase in the spreading of Lucifer yellow through gap junctions to neighboring astrocytes when the cells were patched with intracellular solutions containing 1 mM SPM, a physiological concentration in glia. Lucifer yellow propagation was inhibited by gap junction blockers. Our findings show that the glial syncitium propagates SPM through gap junctions and further indicate a new role of polyamines in the regulation of the astroglial network under both normal and pathological conditions.
Assuntos
Astrócitos/metabolismo , Comunicação Celular/efeitos dos fármacos , Espermidina/fisiologia , Espermina/fisiologia , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/crescimento & desenvolvimento , Carbenoxolona/farmacologia , Conexina 43/fisiologia , Feminino , Corantes Fluorescentes/metabolismo , Junções Comunicantes/efeitos dos fármacos , Junções Comunicantes/metabolismo , Células Gigantes/efeitos dos fármacos , Células Gigantes/metabolismo , Líquido Intracelular/metabolismo , Isoquinolinas/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espermidina/farmacologia , Espermina/farmacologiaRESUMO
The polyamines are ubiquitous polycationic compounds. Over the past 40 yr, investigation has shown that some of these, namely spermine, spermidine, and putrescine, are essential to male and female reproductive processes and to embryo/fetal development. Indeed, their absence is characterized by infertility and arrest in embryogenesis. Mammals synthesize polyamines de novo from amino acids or import these compounds from the diet. Information collected recently has shown that polyamines are essential regulators of cell growth and gene expression, and they have been implicated in both mitosis and meiosis. In male reproduction, polyamine expression correlates with stages of spermatogenesis, and polyamines appear to function in promoting sperm motility. There is evidence for polyamine involvement in ovarian follicle development and ovulation in female mammals, and polyamine synthesis is required for steroidogenesis in the ovary. Studies of the embryo indicate a polyamine requirement that can be met from maternal sources before implantation, whereas elimination of polyamine synthesis abrogates embryo development at gastrulation. Polyamines play roles in embryo implantation, in decidualization, and in placental formation and function, and polyamine privation during gestation results in intrauterine growth retardation. Emerging information implicates dietary arginine and dietary polyamines as nutritional regulators of fertility. The mechanisms by which polyamines regulate these multiple and diverse processes are not yet well explored; thus, there is fertile ground for further productive investigation.
Assuntos
Poliaminas , Reprodução , Animais , Implantação do Embrião , Desenvolvimento Embrionário/fisiologia , Feminino , Fertilização , Hormônios Esteroides Gonadais/fisiologia , Humanos , Masculino , Oogênese , Ovário/fisiologia , Poliaminas/química , Poliaminas/metabolismo , Gravidez , Reprodução/fisiologia , Sêmen , Motilidade dos Espermatozoides , Espermatogênese , Espermidina/biossíntese , Espermidina/química , Espermidina/fisiologia , Espermina/biossíntese , Espermina/química , Espermina/fisiologia , Testículo/fisiologia , Útero/metabolismoRESUMO
Polyamines (PAs) are small metabolites that are produced and oxidized in chloroplasts with an obscure mode of action. Recently, we showed that qE is stimulated by PAs in higher plants (Nicotiana tabacum) and in genetically modified plants with elevated thylakoid-associated PAs (Ioannidis and Kotzabasis Biochim Biophys Acta 1767:1371-1382, 2007; Ioannidis et al. Biochim Biophys Acta 1787:1215-1222, 2009). Here, we investigated further their quenching properties both in vivo in green algae and in vitro is isolated LHCII. In vivo spermine up-regulates NPQ in Scenedesums obliquus about 30%. In vitro putrescine--the obligatory metabolic precursor of PAs--has a marginal quenching effect, while spermidine and spermine exhibit strong quenching abilities in isolated LHCII up to 40%. Based on available 3D models of LHCII we report a special cavity of about 600 Å(3) and a near-by larger pocket in the trimeric LHCII that could be of importance for the stimulation of qE by amines.
Assuntos
Poliaminas Biogênicas/metabolismo , Clorofila/metabolismo , Scenedesmus/metabolismo , Clorofila A , Fluorescência , Complexos de Proteínas Captadores de Luz/química , Complexos de Proteínas Captadores de Luz/metabolismo , Modelos Moleculares , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Proteínas de Plantas/fisiologia , Estrutura Terciária de Proteína , Espermidina/metabolismo , Espermidina/fisiologia , Espermina/metabolismo , Espermina/fisiologiaRESUMO
In recent years, gene expression, genetic association, and metabolic studies have implicated the polyamine system in psychiatric conditions, including suicide. Given the extensive regulation of genes involved in polyamine metabolism, as well as their interconnections with the metabolism of other amino acids, we were interested in further investigating the expression of polyamine-related genes across the brain in order to obtain a more comprehensive view of the dysregulation of this system in suicide. To this end, we examined the expression of genes related to polyamine metabolism across 22 brain regions in a sample of 29 mood-disordered suicide completers and 16 controls, and identified 14 genes displaying differential expression. Among these, altered expression of spermidine/spermine N1-acetyltransferase, spermine oxidase, and spermine synthase, has previously been observed in brains of suicide completers, while the remainder of the genes represent novel findings. In addition to genes with direct involvement in polyamine metabolism, including S-adenosylmethionine decarboxylase, ornithine decarboxylase antizymes 1 and 2, and arginase II, we identified altered expression of several more distally related genes, including aldehyde dehydrogenase 3 family, member A2, brain creatine kinase, mitochondrial creatine kinase 1, glycine amidinotransferase, glutamic-oxaloacetic transaminase 1, and arginyl-tRNA synthetase-like. Many of these genes displayed altered expression across several brain regions, strongly implying that dysregulated polyamine metabolism is a widespread phenomenon in the brains of suicide completers. This study provides a broader view of the nature and extent of the dysregulation of the polyamine system in suicide, and highlights the importance of this system in the neurobiology of suicide.
Assuntos
Perfilação da Expressão Gênica , Transtornos do Humor/genética , Poliaminas/metabolismo , Espermina Sintase/fisiologia , Suicídio , Adenosilmetionina Descarboxilase/genética , Adenosilmetionina Descarboxilase/fisiologia , Aspartato Aminotransferases/genética , Mapeamento Cromossômico , DNA Complementar/análise , Expressão Gênica , Humanos , Masculino , Análise em Microsséries , Transtornos do Humor/fisiopatologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/fisiologia , Espermidina/fisiologia , Espermina Sintase/genética , Poliamina OxidaseRESUMO
Spermidine is a ubiquitous polycation that is synthesized from putrescine and serves as a precursor of spermine. Putrescine, spermidine and spermine all are polyamines that participate in multiple known and unknown biological processes. Exogenous supply of spermidine prolongs the life span of several model organisms including yeast (Saccharomyces cerevisiae), nematodes (Caenorhabditis elegans) and flies (Drosophila melanogaster) and significantly reduces age-related oxidative protein damage in mice, indicating that this agent may act as a universal anti-aging drug. Spermidine induces autophagy in cultured yeast and mammalian cells, as well as in nematodes and flies. Genetic inactivation of genes essential for autophagy abolishes the life span-prolonging effect of spermidine in yeast, nematodes and flies. These findings complement expanding evidence that autophagy mediates cytoprotection against a variety of noxious agents and can confer longevity when induced at the whole-organism level. We hypothesize that increased autophagic turnover of cytoplasmic organelles or long-lived proteins is involved in most if not all life span-prolonging therapies.
Assuntos
Autofagia/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Espermidina/farmacologia , Animais , Autofagia/genética , Sobrevivência Celular/efeitos dos fármacos , Dípteros , Camundongos , Modelos Biológicos , Nematoides , Espermidina/fisiologia , Regulação para Cima/efeitos dos fármacos , LevedurasRESUMO
To verify whether spermidine synthase (SPDS) can confer long-term multi-heavy metal tolerance, in vitro shoots of a transgenic European pear (Pyrus communis L. 'Ballad') line #32 overexpressing apple SPDS (MdSPDS1), as well as a wild type (WT) line, were subjected to stress using either CdCl(2), PbCl(2), ZnCl(2), or a combination thereof. Based on either shoot height increment or fresh weight and morphological changes upon heavy metal stress, the performance of the transgenic line #32 was better than that of WT. Although SPDS expression levels and spermidine (Spd) contents in line #32 were higher than those in WT, possibly due to transgene (MdSPDS1) expression, no obvious inductions of SPDS expression and increases in Spd-content were observed by long-term stress treatments in both lines. When the glutathione (GSH) content was compared with or without stress in each line, GSH was significantly depleted in line #32 with stress, but not as much as in WT. The activities of glutathione reductase and superoxide dismutase and the content of malondialdehyde, an indicator for lipid peroxidation, changed upon stress toward a more favorable status for survival in line #32 than in WT. These antioxidant parameters were positively related to Spd-content. The accumulation of heavy metals tended to be less in line #32 than in WT except for Zn stress, and the Ca content showed an opposite trend. These results suggest that Spd-levels are implicated in enhanced heavy metal tolerance, possibly by exerting an antioxidant activity as well as by the properties of Spd per se including metal chelator.
Assuntos
Tolerância a Medicamentos/genética , Metais Pesados/toxicidade , Pyrus , Espermidina Sintase/genética , Espermidina/fisiologia , Antioxidantes/metabolismo , Antioxidantes/fisiologia , Regulação da Expressão Gênica de Plantas , Glutationa Redutase/metabolismo , Malondialdeído/metabolismo , Brotos de Planta/anatomia & histologia , Brotos de Planta/genética , Brotos de Planta/metabolismo , Plantas Geneticamente Modificadas , Poliaminas/metabolismo , Pyrus/anatomia & histologia , Pyrus/genética , Pyrus/metabolismo , Espermidina/análise , Espermidina/metabolismo , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Polyamines are small polycationic molecules found ubiquitously in all organisms and function in a wide variety of biological processes. In the past decade, molecular and genetic studies using mutants and transgenic plants with an altered activity of enzymes involved in polyamine biosynthesis have contributed much to a better understanding of the biological functions of polyamines in plants. POSSIBLE ROLES: Spermidine is essential for survival of Arabidopsis embryos. One of the reasons may lie in the fact that spermidine serves as a substrate for the lysine hypusine post-translational modification of the eukaryotic translation initiation factor 5A, which is essential in all eukaryotic cells. Spermine is not essential but plays a role in stress responses, probably through the modulation of cation channel activities, and as a source of hydrogen peroxide during pathogen infection. Thermospermine, an isomer of spermine, is involved in stem elongation, possibly by acting on the regulation of upstream open reading frame-mediated translation. CONCLUSIONS: The mechanisms of action of polyamines differ greatly from those of plant hormones. There remain numerous unanswered questions regarding polyamines in plants, such as transport systems and polyamine-responsive genes. Further studies on the action of polyamines will undoubtedly provide a new understanding of plant growth regulation and stress responses.
Assuntos
Plantas/metabolismo , Poliaminas/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Oxirredução , Filogenia , Desenvolvimento Vegetal , Plantas/genética , Putrescina/metabolismo , Putrescina/fisiologia , Espermidina/metabolismo , Espermidina/fisiologia , Espermina/análogos & derivados , Espermina/metabolismo , Espermina/fisiologia , Estresse FisiológicoRESUMO
The polyamines, spermidine and spermine, were first discovered in 1678 by Antonie van Leeuwenhoek. In the early part of the 20th century their structure was determined and their pathway of biosynthesis established. The polyamines are essential elements of cells from all species. They are required for optimum cell growth, and cells where polyamine production has been prevented by mutation, or blocked by inhibitors, require exogenous provision of at least one polyamine for continued survival. Despite this critical function, the polyamines have not attracted as much attention as they deserve in the wider field of biochemistry and cell biology. They are rarely mentioned in standard textbooks, despite over 75000 research papers having been written on the subject since 1900, and more than half (54%) were published after 1990. There have been a number of books dedicated to the polyamines published and "The Guide to the Polyamines" by Seymour Cohen deserves mention as a work of outstanding scholarship describing "everything you ever wanted to know about the polyamines" in exquisite detail. The current volume of Essays in Biochemistry has a much humbler aim: to introduce the polyamines to interested researchers and students, and to describe how they are associated with, and might be utilized as a target for intervention in major diseases such as cancer.
Assuntos
Poliaminas/química , Animais , Bioquímica/história , Bioquímica/tendências , História do Século XVII , História do Século XX , Humanos , Modelos Biológicos , Espermidina/fisiologia , Espermina/fisiologiaRESUMO
Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme of polyamine catabolism. In a previous study, we constructed a recombinant adenovirus, Ad-SSAT, which can express human SSAT. In the present study, we investigated the effect of Ad-SSAT on the growth and cell cycle of colorectal cancer cells. We found that Ad-SSAT increased the expression of SSAT and inhibited the growth of HT-29 and Lovo cells. The growth inhibition was caused by cell cycle arrest in the S phase. Furthermore, Ad-SSAT was shown to suppress the expression of cyclin A and nuclear factor E2F-1 in HT-29 and Lovo cells. The inhibitory effect of Ad-SSAT on cyclin A promoter activity was also observed in a reporter gene assay. Our results suggest that the expression of SSAT mediated by Ad-SSAT infection inhibits the growth of colorectal cancer cells and induces cell cycle arrest at the S phase, through a mechanism involving the suppression of cyclin A and E2F-1 expression.