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1.
Physiol Plant ; 173(4): 2291-2297, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34609746

RESUMO

The plant hormone ethylene plays vital roles in plant development, including pollen tube (PT) growth. Many studies have used the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), as a tool to trigger ethylene signaling. Several studies have suggested that ACC can act as a signal molecule independently of ethylene, inducing responses that are distinct from those induced by ethylene. In this study, we confirmed that ethylene receptor function is essential for promoting PT growth in tomato, but interestingly, we discovered that ACC itself can act as a signal that also promotes PT growth. Exogenous ACC stimulated PT growth even when ethylene perception was inhibited either chemically by treating with 1-methylcyclopropene (1-MCP) or genetically by using the ethylene-insensitive Never Ripe (NR) mutant. Treatment with aminoethoxyvinylglycine, which reduces endogenous ACC levels, led to a reduction of PT growth, even in the NR mutants. Furthermore, GUS activity driven by an EIN3 Binding Site promoter (EBS:GUS transgene) was triggered by ACC in the presence of 1-MCP. Taken together, these results suggest that ACC signaling can bypass the ethylene receptor step to stimulate PT growth and EBS driven gene expression.


Assuntos
Solanum lycopersicum , Aminoácidos Cíclicos/farmacologia , Etilenos , Solanum lycopersicum/genética , Tubo Polínico
2.
Biomolecules ; 11(8)2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34439819

RESUMO

With the introduction of the new auxinic herbicide halauxifen-methyl into the oilseed rape (Brassica napus) market, there is a need to understand how this new molecule interacts with indigenous plant hormones (e.g., IAA) in terms of crop response. The aim of this study was to investigate the molecular background by using different growth conditions under which three different auxinic herbicides were administered. These were halauxifen-methyl (Hal), alone and together with aminopyralid (AP) as well as picloram (Pic). Three different hormone classes were determined, free and conjugated indole-3-acetic acid (IAA), aminocyclopropane carboxylic acid (ACC) as a precursor for ethylene, and abscisic acid (ABA) at two different temperatures and growth stages as well as over time (2-168 h after treatment). At 15 °C growth temperature, the effect was more pronounced than at 9 °C, and generally, the younger leaves independent of the developmental stage showed a larger effect on the alterations of hormones. IAA and ACC showed reproducible alterations after auxinic herbicide treatments over time, while ABA did not. Finally, a transcriptome analysis after treatment with two auxinic herbicides, Hal and Pic, showed different expression patterns. Hal treatment leads to the upregulation of auxin and hormone responses at 48 h and 96 h. Pic treatment induced the hormone/auxin response already after 2 h, and this continued for the other time points. The more detailed analysis of the auxin response in the datasets indicate a role for GH3 genes and genes encoding auxin efflux proteins. The upregulation of the GH3 genes correlates with the increase in conjugated IAA at the same time points and treatments. Also, genes for were found that confirm the upregulation of the ethylene pathway.


Assuntos
Ácido Abscísico/farmacologia , Aminoácidos Cíclicos/farmacologia , Brassica napus/efeitos dos fármacos , Herbicidas/farmacologia , Ácidos Indolacéticos/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Ácido Abscísico/metabolismo , Aminoácidos Cíclicos/metabolismo , Brassica napus/genética , Brassica napus/metabolismo , Ácidos Carboxílicos/farmacologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Ácidos Indolacéticos/metabolismo , Anotação de Sequência Molecular , Picloram/farmacologia , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Piridinas/farmacologia , Temperatura , Transcriptoma
3.
Plant J ; 107(6): 1819-1836, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34296474

RESUMO

Leaf senescence is a pivotal step in the last stage of the plant life cycle and is influenced by various external and endogenous cues. A series of reports have indicated the involvement of the WRKY transcription factors in regulating leaf senescence, but the molecular mechanisms and signaling pathways remain largely unclear. Here we provide evidence demonstrating that WRKY71 acts as a positive regulator of leaf senescence in Arabidopsis. WRKY71-1D, an overexpressor of WRKY71, exhibited early leaf senescence, while wrky71-1, the WRKY71 loss-of-function mutant, displayed delayed leaf senescence. Accordingly, a set of senescence-associated genes (SAGs) were substantially elevated in WRKY71-1D but markedly decreased in wrky71-1. Chromatin immunoprecipitation assays indicated that WRKY71 can bind directly to the promoters of SAG13 and SAG201. Transcriptome analysis suggested that WRKY71 might mediate multiple cues to accelerate leaf senescence, such as abiotic stresses, dark and ethylene. WRKY71 was ethylene inducible, and treatment with the ethylene precursor 1-amino-cyclopropane-1-carboxylic acid enhanced leaf senescence in WRKY71-1D but caused only a marginal delay in leaf senescence in wrky71-1. In vitro and in vivo assays demonstrated that WRKY71 can directly regulate ETHYLENE INSENSITIVE2 (EIN2) and ORESARA1 (ORE1), genes of the ethylene signaling pathway. Consistently, leaf senescence of WRKY71-1D was obviously retarded in the ein2-5 and nac2-1 mutants. Moreover, WRKY71 was also proved to interact with ACS2 in vitro and in vivo. Treatment with AgNO3 and aminoethoxyvinylglycine and acs2-1 could greatly arrest the leaf senescence of WRKY71-1D. In conclusion, our data revealed that WRKY71 mediates ethylene signaling and synthesis to hasten leaf senescence in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Liases de Carbono-Enxofre/genética , Etilenos/metabolismo , Regulação da Expressão Gênica de Plantas , Folhas de Planta/fisiologia , Senescência Vegetal/fisiologia , Fatores de Transcrição/genética , Oxirredutases do Álcool/genética , Aminoácidos Cíclicos/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Imunoprecipitação da Cromatina , Senescência Vegetal/genética , Plantas Geneticamente Modificadas , Regiões Promotoras Genéticas , Receptores de Superfície Celular/genética , Transativadores , Fatores de Transcrição/metabolismo
4.
Endocrinology ; 162(9)2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34134142

RESUMO

Transitional hypoglycemia in normal newborns occurs in the first 3 days of life and has clinical features consistent with hyperinsulinism. We found a lower threshold for glucose-stimulated insulin secretion from freshly isolated embryonic day (E) 22 rat islets, which persisted into the first postnatal days. The threshold reached the adult level by postnatal day (P) 14. Culturing P14 islets also decreased the glucose threshold. Freshly isolated P1 rat islets had a lower threshold for insulin secretion in response to 2-aminobicyclo-(2, 2, 1)-heptane-2-carboxylic acid, a nonmetabolizable leucine analog, and diminished insulin release in response to tolbutamide, an inhibitor of ß-cell KATP channels. These findings suggested that decreased KATP channel function could be responsible for the lower glucose threshold for insulin secretion. Single-cell transcriptomic analysis did not reveal a lower expression of KATP subunit genes in E22 compared with P14 ß cells. The investigation of electrophysiological characteristics of dispersed ß cells showed that early neonatal and cultured cells had fewer functional KATP channels per unit membrane area. Our findings suggest that decreased surface density of KATP channels may contribute to the observed differences in glucose threshold for insulin release.


Assuntos
Glucose/farmacologia , Secreção de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/efeitos dos fármacos , Canais KATP/fisiologia , 1-Metil-3-Isobutilxantina/farmacologia , Aminoácidos Cíclicos/farmacologia , Animais , Animais Recém-Nascidos , Células Cultivadas , Embrião de Mamíferos , Feminino , Glucose/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Canais KATP/agonistas , Canais KATP/genética , Canais KATP/metabolismo , Cloreto de Potássio/farmacologia , Gravidez , Ratos , Ratos Sprague-Dawley
5.
Plant Cell Physiol ; 62(5): 858-871, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33768225

RESUMO

Ethylene is a gaseous phytohormone involved in various physiological processes, including fruit ripening, senescence, root hair development and stress responses. Recent genomics studies have suggested that most homologous genes of ethylene biosynthesis and signaling are conserved from algae to angiosperms, whereas the function and biosynthesis of ethylene remain unknown in basal plants. Here, we examined the physiological effects of ethylene, an ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC) and an inhibitor of ethylene perception, silver thiosulfate (STS), in a basal land plant, Marchantia polymorpha. M. polymorpha plants biosynthesized ethylene, and treatment with high concentrations of ACC slightly promoted ethylene production. ACC remarkably suppressed the growth of thalli (vegetative organs) and rhizoids (root-hair-like cells), whereas exogenous ethylene slightly promoted thallus growth. STS suppressed thallus growth and induced ectopic rhizoid formation on the dorsal surface of thalli. Thus, ACC and ethylene have different effects on the vegetative growth of M. polymorpha. We generated single and double mutants of ACC synthase-like (ACSL) genes, MpACSL1 and MpACSL2. The mutants did not show obvious defects in thallus growth, ACC content and ethylene production, indicating that MpACSL genes are not essential for the vegetative growth and biosynthesis of ACC and ethylene. Gene expression analysis suggested the involvement of MpACSL1 and MpACSL2 in stress responses. Collectively, our results imply ethylene-independent function of ACC and the absence of ACC-mediated ethylene biosynthesis in M. polymorpha.


Assuntos
Aminoácidos Cíclicos/metabolismo , Etilenos/metabolismo , Marchantia/metabolismo , Aminoácidos Cíclicos/farmacologia , Etilenos/biossíntese , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Marchantia/efeitos dos fármacos , Marchantia/genética , Marchantia/crescimento & desenvolvimento , Mutação , Compostos Organofosforados/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tiossulfatos/farmacologia
6.
Chem Phys Lipids ; 235: 105051, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33460592

RESUMO

Novel quaternary ammonium surfactants (QUATs) derived from phenylalaninyl-proline dipeptide with chain length C12 and C14 were synthesised as potential active ingredients to be used in body cleansing formulations. The physicochemical properties and biological activities of the QUATs were determined in both single and in mixed surfactant system with either the conventional anionic surfactant sodium dodecyl sulphate (SDS) or sodium N-dodecyl prolinate. The C12 QUAT derivative showed antagonistic behaviour in both SDS and sodium N-dodecyl prolinate mixed surfactant system. Comparing the mixed system of the C12 QUAT with SDS and sodium N-dodecyl prolinate, it was found that the latter displayed better antibacterial activity together with the lower ocular irritation. The C12 QUAT-sodium N-dodecyl prolinate mixture were non cytotoxic at a concentration corresponding to its MIC value, showing that the mixture was selective towards bacterial cells rather than mammalian cell lines. Diffusion measurements showed that the sodium N-dodecyl prolinate surfactant consisted of 26 molecules per micelle in water but only 3 molecules per micelle in DMSO/water (1:1). On the other hand, C12 QUAT did not form a micelle in DMSO/Water. Membrane permeability studies of the C12 QUAT and sodium N-dodecyl prolinate showed that these surfactants are capable to penetrate into deeper skin layers to exert their antibacterial and cleansing action and hence can be used as a promising candidate as active ingredients in body wash formulations.


Assuntos
Aminoácidos Aromáticos/farmacologia , Aminoácidos Cíclicos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Compostos de Amônio Quaternário/farmacologia , Aminoácidos Aromáticos/química , Aminoácidos Cíclicos/química , Antibacterianos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Tensoativos/química , Tensoativos/farmacologia
7.
Plant Physiol Biochem ; 156: 345-356, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33002713

RESUMO

Although ethylene (ET) is an important participant in plant responses to salt stress, its role in the early period of acclimation, especially in the case of photosynthesis has not been revealed in detail. In this study, the effects of tolerable (100 mM) or lethal (250 mM) NaCl concentrations were investigated in hydroponically grown tomato (Solanum lycopersicum L. cv. Ailsa Craig) plants of different ET status, in wild type (WT) plants, in WT plants pre-treated with the ET generator 1-aminocyclopropane-1-carboxylic acid (ACC) and in ET insensitive, Never ripe (Nr/Nr) mutants for 1-, 6- and 24 h. In the leaves ACC treatment reduced the osmotic effect of salt stress, while Nr mutation enhanced not only osmotic but ionic component of salt stress at 100 mM NaCl. ET insensitivity caused greater decline in stomatal conductance and photosynthetic CO2 assimilation rate than in the controls under tolerable salt stress, but both ACC treatment and Nr mutation helped to maintain positive carbon assimilation under lethal salt stress after 24 h. Nr mutant leaves showed highly enhanced regulated non-photochemical quenching (NPQ) and therefore lower quantum yield of photosystem II (PSII), due to more intensive cyclic electron flow around photosystem I (CEF-PSI), which was further increased under high salinity. Exogenous ACC treatment lowered CEF-PSI and enhanced PSII photochemistry after 6 h of lethal salt stress. Controlling PSI photoinhibition, ET is suggested to be an important regulator of CEF-PSI and photoprotection under salt stress. Furthermore, the altered ET status could cause contrasting effects under different stress severity.


Assuntos
Aminoácidos Cíclicos/farmacologia , Etilenos/metabolismo , Fotossíntese , Estresse Salino , Solanum lycopersicum/fisiologia , Ácidos Carboxílicos , Complexo de Proteína do Fotossistema II/metabolismo , Folhas de Planta/metabolismo
8.
Eur J Med Chem ; 208: 112736, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32966895

RESUMO

Tailor-made AAs are indispensable components of modern medicinal chemistry and are becoming increasingly prominent in new drugs. In fact, about 30% of small-molecule pharmaceuticals contain residues of tailor-made AAs or structurally related diamines and amino-alcohols. Cyclic tailor-made AAs present a particular value to rational structural design by virtue of their local conformational constraints and are widely used in lead optimization programs. The present review article highlights 34 compounds, all of which are derived from cyclic AAs, representing recently-approved, small-molecule pharmaceuticals as well as promising drug candidates currently in various phases of clinical study. For each compound, the discussion includes the discovery, therapeutic profile and optimized synthesis, with a focus on the preparation of cyclic tailor-made AA as the principal structural feature. The present review article is intended to serve as a reference source for organic, medicinal and process chemists along with other professionals working in the fields of drug design and pharmaceutical discovery.


Assuntos
Aminoácidos Cíclicos/química , Preparações Farmacêuticas/química , Aminoácidos Cíclicos/síntese química , Aminoácidos Cíclicos/farmacologia , Animais , Linhagem Celular , Química Farmacêutica , Desenho de Fármacos , Humanos , Preparações Farmacêuticas/síntese química
9.
Mol Biotechnol ; 62(11-12): 557-562, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32949367

RESUMO

The study of senescence preservative on cut flowers helps boost the commercial value of flowers. Senescence in cut flower is associated with an increase of ethylene production, and is significantly influenced by ethylene pathway. This study was conducted to investigate whether S-adenosyl-L-methionine (SAM) and aminocyclopropane-1-carboxylic acid (ACC) involved in the ethylene synthesis process are correlated with the lysosome. The alterations of lysosome which was treated with the ethylene precursors ACC and SAM in HeLa cell using the confocal laser scanning microscope were investigated. According to the experimental results, the activity of lysosomes increased concentration dependently by ACC treatment, however, no change was observed by SAM treatment. In addition, Liquid chromatography-mass spectrometry (LC/MS) analysis was performed to confirm the effect of lysosomal enzyme (LE) extracted from egg white on ACC reduction, but no change was observed. On the contrary, to confirm the effect of ACC on lysosomes, lysosomes were extracted from HeLa cells treated with 5 mM ACC and confirmed by FE-SEM. The results showed that the size of lysosomes treated with ACC is larger than that of the control, which was treated with distilled water. The lysosomes in the control group were distributed in various ranges from 0 to 800 nm, but those treated with 5 mM ACC were in the range of 400 nm to 800 nm or more. Therefore, lysosomes had no effect on ACC, the precursor of ethylene, the aging hormone of cut flowers, however, ACC had effect on lysosomes.


Assuntos
Aminoácidos Cíclicos/farmacologia , Lisossomos/ultraestrutura , S-Adenosilmetionina/farmacologia , Cromatografia Líquida , Células HeLa , Humanos , Lisossomos/efeitos dos fármacos , Espectrometria de Massas , Microscopia Confocal , Tamanho da Partícula
10.
J Med Chem ; 63(14): 7857-7866, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32588620

RESUMO

In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma while preserving its safety. In animal experiments, prodrugs (3e, 3g, and 3j) were significantly better than fospropofol (the only water-soluble propofol prodrug that has been used clinically) in terms of safety, onset, and duration time of anesthesia. Their molar dose, onset time, and anesthesia duration time were comparable to those of propofol, helping to maintain the clinical benefits of propofol. The experimental results showed the potential of such compounds as water-soluble prodrugs of propofol.


Assuntos
Aminoácidos Cíclicos/farmacologia , Anestésicos Intravenosos/farmacologia , Glicolatos/farmacologia , Pró-Fármacos/farmacologia , Propofol/farmacologia , Aminoácidos Cíclicos/síntese química , Anestésicos Intravenosos/síntese química , Animais , Desenho de Fármacos , Glicolatos/síntese química , Masculino , Camundongos , Pró-Fármacos/síntese química , Propofol/síntese química , Solubilidade , Água/química
11.
Plant Mol Biol ; 102(1-2): 143-158, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782079

RESUMO

KEY MESSAGE: Zinc finger protein transcription factor ZFP5 positively regulates root hair elongation in response to Pi and potassium deficiency by mainly activating the expression of EIN2 in Arabidopsis. Phosphate (Pi) and potassium (K+) are major plant nutrients required for plant growth and development, and plants respond to low-nutrient conditions via metabolic and morphology changes. The C2H2 transcription factor ZFP5 is a key regulator of trichome and root hair development in Arabidopsis. However, its role in regulating root hair development under nutrient deprivations remains unknown. Here, we show that Pi and potassium deficiency could not restore the short root hair phenotype of zfp5 mutant and ZFP5 RNAi lines to wild type level. The deprivation of either of these nutrients also induced the expression of ZFP5 and the activity of an ethylene reporter, pEBS:GUS. The significant reduction of root hair length in ein2-1 and ein3-1 as compared to wild-type under Pi and potassium deficiency supports the involvement of ethylene in root hair elongation. Furthermore, the application of 1-aminocyclopropane-1-carboxylic acid (ACC) significantly enhanced the expression level of ZFP5 while the application of 2-aminoethoxyvinyl glycine (AVG) had the opposite effect when either Pi or potassium was deprived. Further experiments reveal that ZFP5 mainly regulates transcription of ETHYLENE INSENSITIVE 2 (EIN2) to control deficiency-mediated root hair development through ethylene signaling. Generally, these results suggest that ZFP5 regulates root hair elongation by interacting with ethylene signaling mainly through regulates the expression of EIN2 in response to Pi and potassium deficiency in Arabidopsis.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Etilenos/metabolismo , Fosfatos/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Deficiência de Potássio/metabolismo , Transdução de Sinais , Aminoácidos Cíclicos/farmacologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Etilenos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Glicina/análogos & derivados , Glicina/farmacologia , Desnutrição/tratamento farmacológico , Mutação , Fenótipo , Raízes de Plantas/efeitos dos fármacos , Deficiência de Potássio/tratamento farmacológico , Interferência de RNA , Receptores de Superfície Celular/metabolismo , Fatores de Transcrição
12.
Sci Rep ; 9(1): 6892, 2019 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053834

RESUMO

Some microbes enhance stress tolerance in plants by minimizing plant ethylene levels via degradation of its immediate precursor, 1-aminocyclopropane-1-carboxylate (ACC), in the rhizosphere. In return, ACC is used by these microbes as a source of nitrogen. This mutualistic relationship between plants and microbes may be used to promote soil properties in stressful environments. In this study, we tested the hypothesis that amendments of ACC in soils reshape the structure of soil microbiome and alleviate the negative impacts of salinity on soil properties. We treated non-saline and artificially-developed saline soils with ACC in different concentrations for 14 days. The structure of soil microbiome, soil microbial properties and productivity were examined. Our results revealed that microbial composition of bacteria, archaea and fungi in saline soils was affected by ACC amendments; whereas community composition in non-saline soils was not affected. The amendments of ACC could not fully counteract the negative effects of salinity on soil microbial activities and productivity, but increased the abundance of ACC deaminase-encoding gene (acdS), enhanced soil microbial respiration, enzymatic activity, nitrogen and carbon cycling potentials and Arabidopsis biomass in saline soils. Collectively, our study indicates that ACC amendments in soils could efficiently ameliorate salinity impacts on soil properties and plant biomass production.


Assuntos
Aminoácidos Cíclicos/farmacologia , Salinidade , Microbiologia do Solo , Solo/química , Actinobacteria/efeitos dos fármacos , Ciclo do Carbono/efeitos dos fármacos , Carbono-Carbono Liases/metabolismo , Fungos/efeitos dos fármacos , Ciclo do Nitrogênio/efeitos dos fármacos
13.
Bioorg Med Chem Lett ; 29(2): 297-301, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30470494

RESUMO

Analogs based on the 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate scaffold showed high potency and selectivity as both group II mGlu receptors orthosteric agonists and antagonists. This scaffold was initially designed to mimic the fully extended glutamate backbone conformation that was hypothesized to be the active conformation for the group II mGlu receptors. With the availability of crystal structures of l-Glu-bound amino terminal domain proteins from multiple mGlu receptor subtypes spanning all three subgroups, a new steric hindrance hypothesis was proposed to account for the scaffold's unique group II selectivity that explores the subtle distance differences between the α-carbon of l-Glu and the center of the tyrosine phenyl ring from the bottom lobe (e.g. Y216 of mGlu2).


Assuntos
Aminoácidos Cíclicos/farmacologia , Ácidos Dicarboxílicos/farmacologia , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Aminoácidos Cíclicos/química , Animais , Ácidos Dicarboxílicos/química , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Ratos , Receptores de Glutamato Metabotrópico/metabolismo , Relação Estrutura-Atividade
14.
Arch Microbiol ; 201(4): 431-442, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30288562

RESUMO

This study aimed to identify Ammodendron bifolium endophytic bacteria, and to evaluate promoting mechanism of selected isolates on seed germination and their effects on host osmotic-stress tolerance. Forty-five strains were isolated from A. bifolium and were classified into 13 different genera by 16S rDNA gene sequence analysis. AY3, AY9 and AG18, which were identified as Staphylococcus, Kocuria, Bacillus sp., promoted host seed ethylene release during germination. Ethrel and 1-aminocyclopropane-1-carboxylic acid (ACC) imitated the effect of AY3, AY9 and AG18 on seed germination. The data suggest that ethylene mediates AY3-, AY9-, AG18-induced A. bifolium seed germination. In addition, osmotic stress prevented seed germination and radicle elongation. However, the inhibitory effect of osmotic stress on seed germination and radicle elongation were rescued by AY3, AY9 and AG18. The results show that AY3, AY9 and AG18 increased osmotic-stress tolerance in A. bifolium. AY3, AY9, AG18 induced A. bifolium seed germination through promoting ethylene production during endophytic bacteria-plant interaction, and increase osmotic-stress tolerance in A. bifolium. AY3, AY9 and AG18 are potential candidates for the protection of A. bifolium.


Assuntos
Fenômenos Fisiológicos Bacterianos , Endófitos/fisiologia , Fabaceae/microbiologia , Germinação , Pressão Osmótica , Aminoácidos Cíclicos/farmacologia , Bactérias/classificação , Bactérias/isolamento & purificação , Endófitos/classificação , Endófitos/isolamento & purificação , Etilenos/metabolismo , Fabaceae/embriologia , Fabaceae/metabolismo , Compostos Organofosforados/farmacologia , Sementes/efeitos dos fármacos , Sementes/metabolismo , Sementes/microbiologia
15.
Genes Genomics ; 40(11): 1237-1248, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30032481

RESUMO

INTRODUCTION: Cellulose microfibril is a major cell wall polymer that plays an important role in the growth and development of plants. The gene cellulose synthase A (CesA), encoding cellulose synthases, is involved in the synthesis of cellulose microfibrils. However, the regulatory mechanism of CesA gene expression is not well understood, especially during the early developmental stages. OBJECTIVE: To identify factor(s) that regulate the expression of CesA genes and ultimately control seedling growth and development. METHODS: The presence of cis-elements in the promoter region of the eight CesA genes identified in flax (Linum usitatissimum L. 'Nike') seedlings was verified, and three kinds of ethylene-responsive cis-elements were identified in the promoters. Therefore, the effect of ethylene on the expression of four selected CesA genes classified into Clades 1 and 6 after treatment with 10-4 and 10-3 M 1-aminocyclopropane-1-carboxylic acid (ACC) was examined in the hypocotyl of 4-6-day-old flax seedlings. RESULTS: ACC-induced ethylene either up- or down-regulated the expression of the CesA genes depending on the clade to which these genes belonged, age of seedlings, part of the hypocotyl, and concentration of ACC. CONCLUSION: Ethylene might be one of the factors regulating the expression of CesA genes in flax seedlings.


Assuntos
Aminoácidos Cíclicos/farmacologia , Etilenos/metabolismo , Linho/genética , Regulação da Expressão Gênica de Plantas , Glucosiltransferases/genética , Linho/efeitos dos fármacos , Linho/crescimento & desenvolvimento , Linho/metabolismo , Glucosiltransferases/classificação , Glucosiltransferases/metabolismo , Hipocótilo/genética , Hipocótilo/metabolismo , Regiões Promotoras Genéticas , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/metabolismo
16.
New Phytol ; 218(3): 999-1014, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29528503

RESUMO

The phytohormone ethylene impacts secondary stem growth in plants by stimulating cambial activity, xylem development and fiber over vessel formation. We report the effect of ethylene on secondary cell wall formation and the molecular connection between ethylene signaling and wood formation. We applied exogenous ethylene or its precursor 1-aminocyclopropane-1-carboxylic acid (ACC) to wild-type and ethylene-insensitive hybrid aspen trees (Populus tremula × tremuloides) and studied secondary cell wall anatomy, chemistry and ultrastructure. We furthermore analyzed the transcriptome (RNA Seq) after ACC application to wild-type and ethylene-insensitive trees. We demonstrate that ACC and ethylene induce gelatinous layers (G-layers) and alter the fiber cell wall cellulose microfibril angle. G-layers are tertiary wall layers rich in cellulose, typically found in tension wood of aspen trees. A vast majority of transcripts affected by ACC are downstream of ethylene perception and include a large number of transcription factors (TFs). Motif-analyses reveal potential connections between ethylene TFs (Ethylene Response Factors (ERFs), ETHYLENE INSENSITIVE 3/ETHYLENE INSENSITIVE3-LIKE1 (EIN3/EIL1)) and wood formation. G-layer formation upon ethylene application suggests that the increase in ethylene biosynthesis observed during tension wood formation is important for its formation. Ethylene-regulated TFs of the ERF and EIN3/EIL1 type could transmit the ethylene signal.


Assuntos
Etilenos/metabolismo , Hibridização Genética , Populus/metabolismo , Transdução de Sinais , Madeira/metabolismo , Aminoácidos Cíclicos/farmacologia , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Parede Celular/ultraestrutura , Celulose/metabolismo , Simulação por Computador , Genes de Plantas , Populus/genética , Populus/ultraestrutura , Análise de Componente Principal , Regiões Promotoras Genéticas/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Água/farmacologia , Madeira/efeitos dos fármacos , Madeira/crescimento & desenvolvimento , Madeira/ultraestrutura , Xilema/efeitos dos fármacos , Xilema/metabolismo , Xilema/ultraestrutura
17.
J Pept Sci ; 24(2)2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29436155

RESUMO

HER2 receptors are surface proteins belonging to the epidermal growth factor family of receptors. Their numbers are elevated in breast, lung, and ovarian cancers. HER2-positive cancers are aggressive, have higher mortality rate, and have a poor prognosis. We have designed peptidomimetics that bind to HER2 and block the HER2-mediated dimerization of epidermal growth factor family of receptors. Among these, a symmetrical cyclic peptidomimetic (compound 18) exhibited antiproliferative activity in HER2-overexpressing lung cancer cell lines with IC50 values in the nanomolar concentration range. To improve the stability of the peptidomimetic, d-amino acids were introduced into the peptidomimetic, and several analogs of compound 18 were designed. Among the analogs of compound 18, compound 32, a cyclic, d-amino acid-containing peptidomimetic, was found to have an IC50 value in the nanomolar range in HER2-overexpressing cancer cell lines. The antiproliferative activity of compound 32 was also measured by using a 3D cell culture model that mimics the in vivo conditions. The binding of compound 32 to the HER2 protein was studied by surface plasmon resonance. In vitro stability studies indicated that compound 32 was stable in serum for 48 hours and intact peptide was detectable in vivo for 12 hours. Results from our studies indicated that 1 of the d-amino acid analogs of 18, compound 32, binds to the HER2 extracellular domain, inhibiting the phosphorylation of kinase of HER2.


Assuntos
Aminoácidos Cíclicos/farmacologia , Antineoplásicos/farmacologia , Biomarcadores Tumorais/antagonistas & inibidores , Peptidomiméticos/farmacologia , Receptor ErbB-2/antagonistas & inibidores , Receptor ErbB-3/antagonistas & inibidores , Sequência de Aminoácidos , Aminoácidos Cíclicos/síntese química , Antineoplásicos/síntese química , Sítios de Ligação , Ligação Competitiva , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Concentração Inibidora 50 , Células MCF-7 , Peptidomiméticos/síntese química , Ligação Proteica , Estabilidade Proteica , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptor ErbB-3/genética , Receptor ErbB-3/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade
18.
Plant Biol (Stuttg) ; 20(3): 490-496, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29350442

RESUMO

Induced systemic resistance (ISR) is one of the indirect mechanisms of growth promotion exerted by plant growth-promoting bacteria, and can be mediated by ethylene (ET). We assessed ET production and the expression of related genes in the Azospirillum-strawberry plant interaction. Ethylene production was evaluated by gas chromatography in plants inoculated or not with A. brasilense REC3. Also, plants were treated with AgNO3 , an inhibitor of ET biosynthesis; with 1-aminocyclopropane-1-carboxylic acid (ACC), a precursor of ET biosynthesis; and with indole acetic acid (IAA). Plant dry biomass and the growth index were determined to assess the growth-promoting effect of A. brasilense REC3 in strawberry plants. Quantitative real time PCR (qRT-PCR) was performed to analyse relative expression of the genes Faetr1, Faers1 and Faein4, which encode ET receptors; Factr1 and Faein2, involved in the ET signalling pathway; Faacs1 encoding ACC synthase; Faaco1 encoding ACC oxidase; and Faaux1 and Faami1 for IAA synthesis enzymes. Results showed that ET acts as a rapid and transient signal in the first 12 h post-treatment. A. brasilense REC3-inoculated plants had a significantly higher growth index compared to control plants. Modulation of the genes Faetr1, Faers1, Faein4, Factr1, Faein2 and Faaco1 indicated activation of ET synthesis and signalling pathways. The up-regulation of Faaux1 and Faami1 involved in IAA synthesis suggested that inoculation with A. brasilense REC3 induces production of this auxin, modulating ET signalling. Ethylene production and up-regulation of genes associated with ET signalling in strawberry plants inoculated with A. brasilense REC3 support the priming activation characteristic of ISR. This type of resistance and the activation of systemic acquired resistance previously observed in this interaction indicate that both are present in strawberry plants, could act synergistically and increase protection against pathogens.


Assuntos
Azospirillum brasilense/metabolismo , Etilenos/metabolismo , Fragaria/microbiologia , Aminoácidos Cíclicos/farmacologia , Biomassa , Etilenos/antagonistas & inibidores , Fragaria/crescimento & desenvolvimento , Fragaria/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Ácidos Indolacéticos/farmacologia , Proteínas de Plantas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/metabolismo , Nitrato de Prata/farmacologia
19.
J Plant Res ; 131(3): 543-554, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29236179

RESUMO

Root hair formation occurs in lettuce seedlings after transfer to an acidic medium (pH 4.0). This process requires cortical microtubule (CMT) randomization in root epidermal cells and the plant hormone ethylene. We investigated the interaction between ethylene and glucose, a new signaling molecule in plants, in lettuce root development, with an emphasis on root hair formation. Dark-grown seedlings were used to exclude the effect of photosynthetically produced glucose. In the dark, neither root hair formation nor the CMT randomization preceding it occurred, even after transfer to the acidic medium (pH 4.0). Adding 1-aminocyclopropane-1-carboxylic-acid (ACC) to the medium rescued the induction, while adding glucose did not. Although CMT randomization occurred when glucose was applied together with ACC, it was somewhat suppressed compared to that in ACC-treated seedlings. This was not due to a decrease in the speed of randomization, but due to lowering of the maximum degree of randomization. Despite the negative effect of glucose on ACC-induced CMT randomization, the density and length of ACC-induced root hairs increased when glucose was also added. The hair-cell length of the ACC-treated seedlings was comparable to that in the combined-treatment seedlings, indicating that the increase in hair density caused by glucose results from an increase in the root hair number. Furthermore, quantitative RT-PCR revealed that glucose suppressed ethylene signaling. These results suggest that glucose has a negative and positive effect on the earlier and later stages of root hair formation, respectively, and that the promotion of the initiation and elongation of root hairs by glucose may be mediated in an ethylene-independent manner.


Assuntos
Aminoácidos Cíclicos/farmacologia , Etilenos/farmacologia , Glucose/farmacologia , Lactuca/efeitos dos fármacos , Reguladores de Crescimento de Plantas/farmacologia , Lactuca/crescimento & desenvolvimento , Microtúbulos/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plântula/efeitos dos fármacos , Plântula/crescimento & desenvolvimento
20.
Amino Acids ; 50(2): 331-340, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29198077

RESUMO

In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to invade joint cartilage, actively contributing to joint destruction in RA. The mechanisms underlying this cell migration and invasion remain unclear. Our previous results and data from the GEO profile indicate that the L-type amino acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with RA were used to determine the effects of suppressing the LAT1 genes using RNA interference and the LAT inhibitor, BCH. We found that BCH exposure reduced the phosphorylation of mTOR and its downstream target 4EBP1, radiolabeled leucine uptake, and migration of RA FLS. LAT1 silencing by siRNA presented effects similar to BCH inhibition. Treatment of cells with IL-17 stimulated the expression of LAT1. In contrast, applying an inhibitor of mTOR pathway, temsirolimus, or silencing eIF4E neutralized the stimulation of IL-17 on LAT1. BCH and siLAT1 also resulted in lower IL-17-stimulated leucine uptake and cell migration. These results suggest that the migration of RA FLS is aggravated by IL-17-mediated overexpression of LAT1 via mTOR/4E-BP1 pathway. In conclusion, further investigation is warranted into LAT1 as a potential target for drug therapies aimed at attenuating migration of transformed-appearing fibroblasts and subsequently preventing further erosion of bone and cartilage.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Fibroblastos/metabolismo , Fosfoproteínas/metabolismo , Membrana Sinovial/patologia , Sinoviócitos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adulto , Idoso , Aminoácidos Cíclicos/farmacologia , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Proteínas de Ciclo Celular , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Fibroblastos/patologia , Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Leucina/análogos & derivados , Leucina/metabolismo , Pessoa de Meia-Idade , Fosfoproteínas/genética , RNA Interferente Pequeno/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sirolimo/análogos & derivados , Sirolimo/farmacologia , Membrana Sinovial/metabolismo , Sinoviócitos/patologia , Serina-Treonina Quinases TOR/antagonistas & inibidores
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