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1.
Gene ; 727: 144230, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31743771

RESUMO

Adverse conditions and biotic strain can lead to significant losses and impose limitations on plant yield. Polyamines (PAs) serve as regulatory molecules for both abiotic/biotic stress responses and cell protection in unfavourable environments. In this work, the transcription pattern of 24 genes orchestrating PA metabolism was investigated in Cucumber Mosaic Virus or Potato Virus Y infected and cold stressed tomato plants. Expression analysis revealed a differential/pleiotropic pattern of gene regulation in PA homeostasis upon biotic, abiotic or combined stress stimuli, thus revealing a discrete response specific to diverse stimuli: (i) biotic stress-influenced genes, (ii) abiotic stress-influenced genes, and (iii) concurrent biotic/abiotic stress-regulated genes. The results support different roles for PAs against abiotic and biotic stress. The expression of several genes, significantly induced under cold stress conditions, is mitigated by a previous viral infection, indicating a possible priming-like mechanism in tomato plants pointing to crosstalk among stress signalling. Several genes and resulting enzymes of PA catabolism were stimulated upon viral infection. Hence, we suggest that PA catabolism resulting in elevated H2O2 levels could mediate defence against viral infection. However, after chilling, the activities of enzymes implicated in PA catabolism remained relatively stable or slightly reduced. This correlates to an increase in free PA content, designating a per se protective role of these compounds against abiotic stress.


Assuntos
Poliaminas Biogênicas/metabolismo , Lycopersicon esculentum/genética , Estresse Fisiológico/genética , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação da Expressão Gênica de Plantas/genética , Homeostase , Peróxido de Hidrogênio/metabolismo , Lycopersicon esculentum/metabolismo , Proteínas de Plantas/genética , Poliaminas/metabolismo , Estresse Fisiológico/fisiologia
2.
J Pharm Biomed Anal ; 177: 112867, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31614303

RESUMO

Gut microbiota, the specific microbial community of the gastrointestinal tract, by means of the production of microbial metabolites provides the host with several functions affecting metabolic and immunological homeostasis. Insights into the intricate relationships between gut microbiota and the host require not only the understanding of its structure and function but also the measurement of effector molecules acting along the gut microbiota axis. This article reviews the literature on targeted chromatographic approaches in analysis of gut microbiota specific metabolites in feces as the most accessible biological matrix which can directly probe the connection between intestinal bacteria and the (patho)physiology of the holobiont. Together with a discussion on sample collection and preparation, the chromatographic methods targeted to determination of some classes of microbiota-derived metabolites (e.g., short-chain fatty acids, bile acids, low molecular masses amines and polyamines, vitamins, neurotransmitters and related compounds) are discussed and their main characteristics, summarized in Tables.


Assuntos
Fezes/química , Microbioma Gastrointestinal/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Metabolômica/métodos , Manejo de Espécimes/métodos , Ácidos e Sais Biliares/análise , Ácidos e Sais Biliares/metabolismo , Cromatografia/métodos , Ácidos Graxos Voláteis/análise , Ácidos Graxos Voláteis/metabolismo , Humanos , Espectrometria de Massas/métodos , Neurotransmissores/análise , Neurotransmissores/metabolismo , Poliaminas/análise , Poliaminas/metabolismo , Vitaminas/análise , Vitaminas/metabolismo
3.
Plant Sci ; 290: 110274, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31779908

RESUMO

Plants are exposed to a vast array of pathogens. The interaction between them may be classified in compatible and incompatible. Polyamines (PAs) are involved in defense responses, as well as salicylic acid (SA), gentisic acid (GA) and nitric oxide (NO), which can increase the content of reactive oxygen species (ROS), creating a harsh environment to the pathogen. ROS can also damage the host cell and they can be controlled by ascorbate and glutathione. Among phytopathogens, one of the major threats to tomato crops is tomato mottle mosaic virus (ToMMV). Resistance against this virus probably involves the Tm-22 gene. This work aimed to analyze signaling and antioxidant molecules in the defense response against ToMMV in Solanum pimpinellifolium and in S. lycopersicum 'VFNT'. In S. pimpinellifolium plants inoculated with ToMMV, an increase in NO, SA, GA, ascorbate and oxidized glutathione and a decrease in the content of PAs were observed. Characteristic symptoms of diseased plants and high absorbance values in PTA-ELISA indicated a compatible interaction. In VFNT-inoculated plants, less significant differences were noticed. Symptoms and viral concentration were not detected, indicating an incompatible interaction, possibly associated with the effector-triggered immunity (ETI) response.


Assuntos
Antioxidantes/metabolismo , Doenças das Plantas/microbiologia , Solanum/metabolismo , Tobamovirus/fisiologia , Gentisatos/metabolismo , Lycopersicon esculentum/metabolismo , Lycopersicon esculentum/microbiologia , Óxido Nítrico/metabolismo , Poliaminas/metabolismo , Ácido Salicílico/metabolismo , Transdução de Sinais , Solanum/microbiologia
4.
PLoS One ; 14(12): e0216513, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31877139

RESUMO

BACKGROUND: Paraquat is one of the most effective herbicides used to control weeds in agricultural management, while the pernicious weed goosegrass (Eleusine indica) has evolved resistance to herbicides, including paraquat. Polyamines provide high-level paraquat resistance in many plants. In the present study, we selected three polyamines, namely, putrescine, spermidine, and spermine, as putative genes to investigate their correlation with paraquat resistance by using paraquat-resistant (R) and paraquat-susceptible (S) goosegrass populations. RESULTS: There was no significant difference in the putrescine nor spermine content between the R and S biotypes. However, 30 and 90 min after paraquat treatment, the spermidine concentration was 346.14-fold and 421.04-fold (P < 0.001) higher in the R biotype than in the S biotype, but the spermidine concentration was drastically reduced to a marginal level after 90 min. Since the transcript level of PqE was low while the spermidine concentration showed a transient increase, the PqE gene was likely involved in the synthesis of the paraquat resistance mechanism, regulation of polyamine content, and synthesis of spermidine and spermine. PqTS1, PqTS2, and PqTS3 encode transporter proteins involved in the regulation of paraquat concentration but showed different transcription patterns with synchronous changes in polyamine content. CONCLUSION: Endogenous polyamines (especially spermidine) play a vital role in paraquat resistance in goosegrass. PqE, PqTS1, PqTS2, and PqTS3 were speculated on the relationship between polyamine metabolism and paraquat resistance. To validate the roles of PqE, PqTS1, PqTS2, and PqTS3 in polyamine transport systems, further research is needed.


Assuntos
Resistência a Medicamentos/fisiologia , Eleusine/genética , Herbicidas/metabolismo , Resistência a Medicamentos/genética , Eleusine/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Paraquat/metabolismo , Poliaminas/metabolismo , Putrescina/metabolismo , Espermidina/metabolismo , Espermina/metabolismo
5.
Chem Commun (Camb) ; 55(99): 14968-14971, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31776519

RESUMO

Micelle-forming amphiphilic drug conjugates were synthesized starting from a biologically active epipodophyllotoxin derivative which was covalently inserted in between a hydrophilic targeting spermine unit, and a hydrophobic stearyl chain. The amphiphilic drug conjugates were further assembled into the corresponding micelles and evaluated in vitro for the active targeting of tumor cells overexpressing the polyamine transport system.


Assuntos
Micelas , Nanoestruturas , Podofilotoxina/química , Poliaminas/metabolismo , Transporte Biológico , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas
6.
BMC Plant Biol ; 19(1): 414, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31590646

RESUMO

BACKGROUND: Melatonin is a pleiotropic signaling molecule that plays multifarious roles in plants stress tolerance. The polyamine (PAs) metabolic pathway has been suggested to eliminate the effects of environmental stresses. However, the underlying mechanism of how melatonin and PAs function together under heat stress largely remains unknown. In this study, we investigated the potential role of melatonin in regulating PAs and nitric oxide (NO) biosynthesis, and counterbalancing oxidative damage induced by heat stress in tomato seedlings. RESULTS: Heat stress enhanced the overproduction of reactive oxygen species (ROS) and damaged inherent defense system, thus reduced plant growth. However, pretreatment with 100 µM melatonin (7 days) followed by exposure to heat stress (24 h) effectively reduced the oxidative stress by controlling the overaccumulation of superoxide (O2•-) and hydrogen peroxide (H2O2), lowering the lipid peroxidation content (as inferred based on malondialdehyde content) and less membrane injury index (MII). This was associated with increased the enzymatic and non-enzymatic antioxidants activities by regulating their related gene expression and modulating the ascorbate-glutathione cycle. The presence of melatonin induced respiratory burst oxidase (RBOH), heat shock transcription factors A2 (HsfA2), heat shock protein 90 (HSP90), and delta 1-pyrroline-5-carboxylate synthetase (P5CS) gene expression, which helped detoxify excess ROS via the hydrogen peroxide-mediated signaling pathway. In addition, heat stress boosted the endogenous levels of putrescine, spermidine and spermine, and increased the PAs contents, indicating higher metabolic gene expression. Moreover, melatonin-pretreated seedlings had further increased PAs levels and upregulated transcript abundance, which coincided with suppression of catabolic-related genes expression. Under heat stress, exogenous melatonin increased endogenous NO content along with nitrate reductase- and NO synthase-related activities, and expression of their related genes were also elevated. CONCLUSIONS: Melatonin pretreatment positively increased the heat tolerance of tomato seedlings by improving their antioxidant defense mechanism, inducing ascorbate-glutathione cycle, and reprogramming the PAs metabolic and NO biosynthesis pathways. These attributes facilitated the scavenging of excess ROS and increased stability of the cellular membrane, which mitigated heat-induced oxidative stress.


Assuntos
Lycopersicon esculentum/metabolismo , Melatonina/metabolismo , Óxido Nítrico/metabolismo , Poliaminas/metabolismo , Plântula/metabolismo , Temperatura Alta , Oxirredução , Estresse Oxidativo/fisiologia
7.
mSphere ; 4(5)2019 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578245

RESUMO

Colibactin is a polyketide/nonribosomal peptide produced by Escherichia coli strains that harbor the pks island. This toxin induces DNA double-strand breaks and DNA interstrand cross-links in infected eukaryotic cells. Colibactin-producing strains are found associated with colorectal cancer biopsy specimens and promote intestinal tumor progression in various murine models. Polyamines are small polycationic molecules produced by both microorganisms and eukaryotic cells. Their levels are increased in malignancies, where they contribute to disease progression and metastasis. In this study, we demonstrated that the endogenous spermidine synthase SpeE is required for full genotoxic activity of colibactin-producing E. coli Supplying spermidine in a ΔspeE pks + E. coli strain restored genotoxic activity. Spermidine is involved in the autotoxicity linked to colibactin and is required for direct damaging activity on DNA. The production of the colibactin prodrug motif is impaired in ΔspeE mutants. Therefore, we demonstrated that spermidine has a direct impact on colibactin synthesis.IMPORTANCE Colibactin-producing Escherichia coli strains are associated with cancerous and precancerous colorectal tissues and are suspected of promoting colorectal carcinogenesis. In this study, we describe a new interplay between the synthesis of the genotoxin colibactin and the polyamine spermidine. Polyamines are highly abundant in cancer tissue and are associated with cell proliferation. The need for spermidine in genotoxic activity provides a new perspective on the role of these metabolites in the pathogenicity of colibactin-producing E. coli strains in colorectal cancer.


Assuntos
Escherichia coli/patogenicidade , Mutagênicos/metabolismo , Peptídeos/metabolismo , Policetídeos/metabolismo , Espermidina Sintase/metabolismo , Espermidina/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Células HeLa , Humanos , Mutação , Poliaminas/metabolismo , Espermidina Sintase/genética
8.
Exp Mol Pathol ; 111: 104316, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31629728

RESUMO

Advances in our understanding of the metabolism and molecular functions of arginine and their alterations in cancer have led to resurgence in the interest of targeting arginine catabolism as an anticancer strategy. Therefore, arginase inhibitors have been proposed as a way to treat cancer. In this study, the anti-tumor potential of the arginase inhibition by NG-hydroxy-nor-L-arginine (nor-NOHA) (3 mg/kg/day, i.p.), administered for 5 weeks (parallel tumors development, every 3th day) against 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary carcinogenesis in rats has been investigated. Treatment by nor-NOHA has obvious inhibition effects on development of carcinogenesis in rats was shown. That was seen in downregulation of rats' tumors size and number, mortality rate, in stopped alteration of tissue histopathology, in decrease of polyamines, NO and MDA (malondialdeide) concentrations (in blood). Results have shown arginase and NO-synthase can cooperate to restrain quantities of polyamines and NO for cancer progression. The results obtained can serve as a base to use this model for determination of productive, noncytotoxic antitumor and immune modulating concentration of anticancer agents. Perspectives of targeting arginase and NOS in cancer management can ground application in clinical medicine.


Assuntos
Antineoplásicos/farmacologia , Arginina/análogos & derivados , Neoplasias da Mama/tratamento farmacológico , 9,10-Dimetil-1,2-benzantraceno/toxicidade , Animais , Arginase/antagonistas & inibidores , Arginase/metabolismo , Arginina/farmacologia , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Mortalidade , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Poliaminas/metabolismo , Ratos Wistar
9.
Sheng Li Xue Bao ; 71(5): 681-688, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31646321

RESUMO

Polyamines (putrescine, spermidine, and spermine) are essential polycations that play important roles in various physiological and pathophysiological processes in mammalian cells. The study was to investigate their role in cardioprotection against ischemia/reperfusion (I/R) injury and the underlying mechanism. Isolated hearts from male Sprague-Dawley rats were Langendorff-perfused and cardiac I/R was achieved by 30 min of global ischemia followed by 120 min of reperfusion. Different concentrations of polyamines (0.1, 1, 10, and 15 µmol/L of putrescine, spermidine, and spermine), cyclosporin A (0.2 µmol/L), or atractyloside (20 µmol/L) were given 10 min before the onset of reperfusion. The hemodynamics were monitored; the lactate dehydrogenase (LDH) levels in the coronary effluent were measured spectrophotometrically; infarct size was determined by the 2,3,5-triphenyltetrazolium chloride staining method; and mitochondrial permeability transition pore (MPTP) opening was determined spectrophotometrically by the Ca2+-induced swelling of isolated cardiac mitochondria. The results showed that compared to I/R alone, 0.1 and 1 µmol/L polyamines treatment improved heart function, reduced LDH release, decreased infarct size, and these effects were inhibited by atractyloside (MPTP activator). In isolated mitochondria from normal rats, 0.1 and 1 µmol/L polyamines treatment inhibited MPTP opening. However, 10 and 15 µmol/L polyamines treatment had the opposite effects, and these effects were inhibited by cyclosporin A (MPTP inhibitor). Our findings showed that polyamines may have either protective or damaging effects on hearts suffering from I/R by inhibiting or activating MPTP opening.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Poliaminas/metabolismo , Animais , Ciclosporina/farmacologia , Masculino , Mitocôndrias Cardíacas/fisiologia , Ratos , Ratos Sprague-Dawley
10.
Nat Rev Cancer ; 19(11): 625-637, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31515518

RESUMO

Methionine uptake and metabolism is involved in a host of cellular functions including methylation reactions, redox maintenance, polyamine synthesis and coupling to folate metabolism, thus coordinating nucleotide and redox status. Each of these functions has been shown in many contexts to be relevant for cancer pathogenesis. Intriguingly, the levels of methionine obtained from the diet can have a large effect on cellular methionine metabolism. This establishes a link between nutrition and tumour cell metabolism that may allow for tumour-specific metabolic vulnerabilities that can be influenced by diet. Recently, a number of studies have begun to investigate the molecular and cellular mechanisms that underlie the interaction between nutrition, methionine metabolism and effects on health and cancer.


Assuntos
Dieta , Metionina/metabolismo , Neoplasias/metabolismo , Medicina de Precisão , Animais , Carbono/metabolismo , Metilação de DNA , Epigênese Genética , Ácido Fólico/metabolismo , Deleção de Genes , Histonas/química , Humanos , Ciências da Nutrição , Oxirredução , Poliaminas/metabolismo , RNA/química
11.
Chemosphere ; 236: 124830, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549671

RESUMO

Polyamines (PAs) are recognized as plant growth regulators that are involved in the stress management in various crops. In the current study, mitigative roles of spermidine (Spd) and putrescine (Put) were assessed in manganese (Mn) stressed Brassica juncea plants. Spd or Put (1.0 mM) were applied to the foliage of Brassica juncea at 35 days after sowing (DAS) grown in the presence of Mn (30 or 150 mg kg-1 soil). The higher level of Mn (150 mg kg-1) diminished photosynthetic attributes and growth, enhanced the production of reactive oxygen species (ROS) like hydrogen peroxide (H2O2) and superoxide anion ( [Formula: see text] ) content, affected stomatal movement and increased the Mn concentration in roots and shoots of the plant at 45 DAS, whereas it enhanced the activities of various antioxidant enzymes and proline content in the foliage of Brassica juncea plants. On the other hand, treatment of PAs (Spd or Put) to Mn stressed as well as non-stressed plants resulted in a remarkable improvement in the stomatal behaviour, photosynthetic attributes, growth and biochemical traits, decreased the production of ROS (H2O2 and [Formula: see text] ) and concentration of Mn in different parts of plant. It is concluded that out of the two polyamines (Spd or Put), Spd proved more efficient and enhanced growth, photosynthesis, and metabolic state of the plants which bestowed tolerance and helped the plants to cope efficiently under Mn stress.


Assuntos
Antioxidantes/farmacologia , Manganês/toxicidade , Mostardeira/química , Fotossíntese , Poliaminas/farmacologia , Antioxidantes/metabolismo , Peróxido de Hidrogênio/metabolismo , Manganês/farmacologia , Mostardeira/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Poliaminas/metabolismo , Putrescina/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espermidina/farmacologia
12.
Int J Mol Sci ; 20(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561575

RESUMO

Acute kidney injury (AKI) refers to an abrupt decrease in kidney function. It affects approximately 7% of all hospitalized patients and almost 35% of intensive care patients. Mortality from acute kidney injury remains high, particularly in critically ill patients, where it can be more than 50%. The primary causes of AKI include ischemia/reperfusion (I/R), sepsis, or nephrotoxicity; however, AKI patients may present with a complicated etiology where many of the aforementioned conditions co-exist. Multiple bio-markers associated with renal damage, as well as metabolic and signal transduction pathways that are involved in the mediation of renal dysfunction have been identified as a result of the examination of models, patient samples, and clinical data of AKI of disparate etiologies. These discoveries have enhanced our ability to diagnose AKIs and to begin to elucidate the mechanisms involved in their pathogenesis. Studies in our laboratory revealed that the expression and activity of spermine/spermidine N1-acetyltransferase (SAT1), the rate-limiting enzyme in polyamine back conversion, were enhanced in kidneys of rats after I/R injury. Additional studies revealed that the expression of spermine oxidase (SMOX), another critical enzyme in polyamine catabolism, is also elevated in the kidney and other organs subjected to I/R, septic, toxic, and traumatic injuries. The maladaptive role of polyamine catabolism in the mediation of AKI and other injuries has been clearly demonstrated. This review will examine the biochemical and mechanistic basis of tissue damage brought about by enhanced polyamine degradation and discuss the potential of therapeutic interventions that target polyamine catabolic enzymes or their byproducts for the treatment of AKI.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/metabolismo , Poliaminas/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo , Animais , Biomarcadores , Expressão Gênica , Regulação Enzimológica da Expressão Gênica , Humanos , Redes e Vias Metabólicas , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/metabolismo
13.
Urologiia ; (4): 74-79, 2019 Sep.
Artigo em Russo | MEDLINE | ID: mdl-31535809

RESUMO

The aim of the study was to compare the content of polyamines (spermine and spermidine) in the seminal plasma of men of different fertility and to reveal the relationship between their level in sperm and the presence of markers of apoptosis in gametes. MATERIALS AND METHODS: ejaculates of 34 fertile men and 40 infertile men with various forms of subfertility between the ages of 22 and 40 were examined. The determination of polyamines was carried out by electrophoretic fractionation in an agar gel. As markers of apoptosis, externalization of phosphatidylserine (PS) to the external side of the spermatozoon membrane was determined and the receptor for the initiation of apoptosis CD95 in the gametes was detected. RESULTS: In sperm of infertile men, more spermatozoa with markers of apoptosis were revealed in comparison with fertile donors (p0,001). Against the background of a general decrease in the concentration of polyamines in ejaculates of infertile patients, the ratio between polyamines with a predominance of sperm in the seminal fluid is observed, which is the initiating factor for the initiation of apoptosis in gametes. This was proved by the relationship between the externalization of FS in gametes and the concentration of sperm in the spermoplasm in accordance with the coefficient of positive correlation (r=0.5, p<0.01). CONCLUSIONS: Thus, a change in the concentration of polyamines in the seminal fluid of men is one of the factors in the regulation of apoptosis of the sex cells. Determination of the content of polyamines in seminal plasma can be recommended to increase the information content of the study of the causes of impaired fertility of the ejaculate, and the results obtained for the development of the algorithm for examining infertile patients.


Assuntos
Infertilidade Masculina , Poliaminas/metabolismo , Adulto , Apoptose , Fertilidade , Humanos , Masculino , Sêmen , Espermatozoides , Adulto Jovem
14.
Plant Physiol Biochem ; 143: 129-141, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493673

RESUMO

Plants respond to Cadmium (Cd) as a hazardous heavy metal through various mechanisms depending on their available metabolite resources. In this research, the physiological and signaling pathways mediating the responses to Cd stress in Scrophularia striata seedlings were characterized after they were exposed to different Cd concentrations at different time periods. The results showed that the polyamines (PAs), Abscisic acid (ABA) and hydrogen peroxide (H2O2) contents were significantly enhanced at 48 h. Moreover, the enzyme activity of phenylalanine ammonia-lyase (PAL) and tyrosine ammonia-lyase (TAL) as regulator enzymes in the phenylpropanoid pathway was increased, related to the reinforcement of phenolic compounds such as phenylethanoid glycosides (as a special compound of this plant). This metabolic profiling indicates that the signal transduction of Cd stress increased the activity of different enzymes (PAL and TAL) by regulating the PAs metabolism, the modulation of ABA, and the H2O2 content. As a result, it caused the accumulation of phenolic compounds, especially echinacoside and acteoside, both of which are required to improve the response of Cd stress in S. striata.


Assuntos
Cádmio/toxicidade , Glicosídeos/metabolismo , Peróxido de Hidrogênio/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Poliaminas/metabolismo , Scrophularia/metabolismo , Scrophularia/efeitos dos fármacos
15.
Eur J Med Chem ; 182: 111666, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494476

RESUMO

Polycation carriers hold great potential in gene therapy. However, they usually suffer from obvious cytotoxicity and unsatisfactory transfection efficiency. In this report, a series of fluorobenzene substituted and thioacetal contained polycations (TAEA-S-xF) were prepared to explore novel alternatives for safe and efficient non-viral polymeric gene vectors. The reactive oxygen species (ROS)-responsive property of thioacetal moieties together with the fluorine effect were hope to bring the vector better performance in gene delivery process. These materials could efficiently condense DNA into nanoparticles with proper size and surface potential. The structure-activity relationship of these materials was systematically investigated, and the In vitro transfection results revealed that the amount of fluorine atoms on the linkage plays important role to ensure the transfection efficiency and serum tolerance. The ROS-responsive behavior was verified by NMR, gel electrophoresis experiment and dynamic light scattering (DLS) assay. Cytotoxicity assay results also suggest that these ROS-degradable polycations show good biocompatibility in response to higher ROS level in cancer cells. Among these fluorinated polymers, the one with the most fluorine atoms showed the best transfection efficiency, which was up to 54 times higher than polyethyleneimine (PEI) 25 kDa. Mechanism studies reveal that its better performance may come from good cellular uptake and endosome escape ability.


Assuntos
Técnicas de Transferência de Genes , Vetores Genéticos/química , Poliaminas/química , Polietilenoimina/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Células CHO , Cricetulus , Relação Dose-Resposta a Droga , Flúor/química , Flúor/metabolismo , Vetores Genéticos/síntese química , Vetores Genéticos/metabolismo , Halogenação , Humanos , Estrutura Molecular , Células PC-3 , Poliaminas/síntese química , Poliaminas/metabolismo , Polietilenoimina/síntese química , Polietilenoimina/metabolismo , Relação Estrutura-Atividade
16.
Plant Physiol Biochem ; 143: 94-108, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31491704

RESUMO

During recent decades, the southern and eastern regions of Asia have experienced high levels of atmospheric N deposition. Excess N deposition is predicted to influence tree growth and species composition in the regions, but visual or physiological assessments alone are not sufficient to determine the real effects of atmospheric N deposition. In this study, we simulated atmospheric wet deposition of inorganic N by spraying a NO3- solution (20 mmol⋅L-1) or a mixture of NO3- (20 mmol⋅L-1) plus NO2- (100 or 300 µmol⋅L-1) on leaves of hybrid poplar (Populus alba × Populus berolinensis) seedlings and examined morphoanatomical traits and physiological processes. Leaves of seedlings sprayed with single or mixed N solutions developed marginal necrosis, curling, and small cracks on the adaxial surface. The silicon (Si)-rich crystals were larger (about 100% increase in crystal diameter compared to untreated seedlings) on the adaxial leaf surface, with a significant positive correlation between the atomic percentage of N and Si on the crystal areas of the surface. Leaves were sensitive to NO2- compared with NO3- even at a low concentration; water content, dry mass, and photochemical variables significantly declined and dark respiration increased only in leaves treated with mixed N form. Mixed N foliar applications significantly increased leaf concentrations of the free amino acids Glu, Gln, and Asn and organic acids oxaloacetic acid and citric acid. Besides, mixed N treatment stimulated leaf transamination, as indicated by significant increases in Ala and Asp concentrations and activities of glutamic oxalacetic transaminase and glutamic pyruvic transaminase. However, mixed N applications led to declines in leaf concentrations of putrescine (by 65%, p = 0.01) and spermine (by 53%, p = 0.01). A higher proportion of NO2- (300 µmol⋅L-1) in mixed N solution was inhibitory to key N-metabolic enzymes and N translocation via the phloem. Our results showed that wet deposition of airborne N pollutants modified surface properties and induced additional detrimental effects related to N-compound foliar absorption. Furthermore, our findings indicate that detoxification of reactive N is apparently related to N assimilation and export from the treated leaves via the phloem.


Assuntos
Nitrogênio/metabolismo , Folhas de Planta/metabolismo , Populus/metabolismo , Plântula/metabolismo , Aminoácidos/metabolismo , Poliaminas/metabolismo
17.
Nat Commun ; 10(1): 3546, 2019 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-31391464

RESUMO

Polyamines are essential for the growth of eukaryotic cells and can be dysregulated in tumors. Here we describe a strategy to deplete polyamines through host-guest encapsulation using a peptide-pillar[5]arene conjugate (P1P5A, P1 = RGDSK(N3)EEEE) as a supramolecular trap. The RGD in the peptide sequence allows the molecule to bind to integrin αvß3-overexpressing tumor cells. The negative charged glutamic acid residues enhance the inclusion affinities between the pillar[5]arene and cationic polyamines via electrostatic interactions and facilitate the solubility of the conjugate in aqueous media. The trap P1P5A efficiently encapsulates polyamines with association constants of 105-106 M-1. We show that P1P5A has a wide spectrum of antitumor activities, and induces apoptosis via affecting the polyamine biosynthetic pathway. Experiments in vivo show that P1P5A effectively inhibits the growth of breast adenocarcinoma xenografts in female nude mice. This work reveals an approach for suppressing tumor growth by using supramolecular macrocycles to trap polyamines in tumor cells.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Poliaminas/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Vias Biossintéticas/efeitos dos fármacos , Neoplasias da Mama/patologia , Calixarenos/química , Calixarenos/farmacologia , Calixarenos/uso terapêutico , Cátions/química , Cátions/metabolismo , Feminino , Humanos , Integrina alfaVbeta3/metabolismo , Células MCF-7 , Camundongos , Camundongos Nus , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/uso terapêutico , Poliaminas/química , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Genes (Basel) ; 10(8)2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405132

RESUMO

We reported changes in the co-regulated mRNA expression in iron walnut (Juglans sigillata) in response to soil pH treatments and identified mRNAs specific to acidic soil conditions. Phenotypic and physiological analyses revealed that iron walnut growth was greater for the pH 4-5 and pH 5-6 treatments than for the pH 3-4 and pH 6-7 treatments. A total of 2768 differentially expressed genes were detected and categorized into 12 clusters by Short Time-series Expression Miner (STEM). The 994 low-expression genes in cluster III and 255 high-expression genes in cluster X were classified as acid-responsive genes on the basis of the relationships between phenotype, physiology, and STEM clustering, and the two gene clusters were analyzed by a maximum likelihood (ML) evolutionary tree with the greatest log likelihood values. No prominent sub-clusters occurred in cluster III, but three occurred in cluster X. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that acid-responsive genes were related primarily to arginine biosynthesis and the arginine/proline metabolism pathway, implying that polyamine accumulation may enhance iron walnut acid stress tolerance. Overall, our results revealed 1249 potentially acid-responsive genes in iron walnut, indicating that its response to acid stress involves different pathways and activated genes.


Assuntos
Genes de Plantas , Juglans/genética , Poliaminas/metabolismo , Estresse Fisiológico , Transcriptoma , Ácidos/análise , Ácidos/farmacologia , Regulação da Expressão Gênica de Plantas , Juglans/efeitos dos fármacos , Juglans/metabolismo , Solo/química
19.
Nature ; 572(7768): 249-253, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31367038

RESUMO

Both single and multicellular organisms depend on anti-stress mechanisms that enable them to deal with sudden changes in the environment, including exposure to heat and oxidants. Central to the stress response are dynamic changes in metabolism, such as the transition from the glycolysis to the pentose phosphate pathway-a conserved first-line response to oxidative insults1,2. Here we report a second metabolic adaptation that protects microbial cells in stress situations. The role of the yeast polyamine transporter Tpo1p3-5 in maintaining oxidant resistance is unknown6. However, a proteomic time-course experiment suggests a link to lysine metabolism. We reveal a connection between polyamine and lysine metabolism during stress situations, in the form of a promiscuous enzymatic reaction in which the first enzyme of the polyamine pathway, Spe1p, decarboxylates lysine and forms an alternative polyamine, cadaverine. The reaction proceeds in the presence of extracellular lysine, which is taken up by cells to reach concentrations up to one hundred times higher than those required for growth. Such extensive harvest is not observed for the other amino acids, is dependent on the polyamine pathway and triggers a reprogramming of redox metabolism. As a result, NADPH-which would otherwise be required for lysine biosynthesis-is channelled into glutathione metabolism, leading to a large increase in glutathione concentrations, lower levels of reactive oxygen species and increased oxidant tolerance. Our results show that nutrient uptake occurs not only to enable cell growth, but when the nutrient availability is favourable it also enables cells to reconfigure their metabolism to preventatively mount stress protection.


Assuntos
Antioxidantes/metabolismo , Lisina/metabolismo , Poliaminas/metabolismo , Saccharomyces cerevisiae/metabolismo , Antiporters/metabolismo , Cadaverina/metabolismo , Glutamina/metabolismo , Glutationa/metabolismo , NADP/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ornitina Descarboxilase/metabolismo , Oxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo
20.
Radiat Res ; 192(3): 324-330, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31298612

RESUMO

The production of 2-deoxyribonolactones (C1'-oxidation product), C4'-oxidized abasic sites and C5'-carbonyl terminated strand scission products was investigated in complexes of double-stranded DNA with protamine, poly-L-lysine and spermine exposed to X-ray radiation. The lesions were quantified by high-performance liquid chromatography through the release of the corresponding low-molecular-weight products 5-methylenefuran-2(5H)-one, N-(2'-hydroxy-ethyl)-5-methylene-D3-pyrrolin-2-one and furfural, respectively. All binders were found to increase the relative yield of C1' oxidation up to 40% of the total 2-deoxyribose damage through the indirect effect versus approximately 18% typically found in homogeneous solutions by the same technique. On the contrary, the yield of C5'-oxidation was found to be suppressed almost completely, while in homogeneous solutions it constituted approximately 14% of the total. The observed change in end product distribution is attributed to free valence transfer to and from the complexing agent, although the mechanisms associated with this process remain unclear.


Assuntos
Dano ao DNA/efeitos da radiação , Peptídeos/metabolismo , Poliaminas/metabolismo , Açúcares Ácidos/metabolismo , Oxirredução/efeitos da radiação
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