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1.
Pestic Biochem Physiol ; 168: 104634, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32711768

RESUMO

Multiple-herbicide resistance (MHR) in barnyardgrass (Echinochloa crus-galli) is a threat to rice production. The Ala-205-Val mutation in acetolactate synthase (ALS) conferred resistance to several ALS inhibitors in the E. crus-galli population AXXZ-2; consequently, ALS-inhibitors were unable to control this noxious weed species. In the present study, the sensitivity to acetyl-coenzyme A carboxylase (ACCase) herbicides and other herbicides having different modes of action was evaluated to determine an effective strategy for chemical weed control. Compared with that of the reportedly sensitive population JLGY-3, the AXXZ-2 population showed differential resistance to three ACCase-inhibitors (cyhalofop-butyl, fenoxaprop-P-ethyl, and pinoxaden), in addition to quinclorac and pretilachlor. A novel substitution (Asp-2078-Glu) in ACCase was detected as the main target-site resistance mechanisms in the AXXZ-2 population. Structural modeling of the mutant ACCase protein predicted that Asp-2078-Glu confers resistance to three ACCase inhibitors by reducing the binding affinity between them and the ACCase protein. To the best of our knowledge, this is the first study to report that the novel Asp-2078-Glu mutation confers resistance to several ACCase inhibitors. Target-site mutations in ALS and ACCase were detected in this MHR population. Except for quinclorac, pretilachlor, ALS inhibitors, and the three ACCase inhibitors, a number of herbicides remain effective in controlling this MHR E. crus-galli population.


Assuntos
Echinochloa/efeitos dos fármacos , Herbicidas/farmacologia , Acetil-CoA Carboxilase/genética , Resistência a Herbicidas , Mutação , Proteínas de Plantas/genética
2.
Pest Manag Sci ; 76(11): 3800-3805, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32476196

RESUMO

BACKGROUND: Asia minor bluegrass (Polypogon fugax) is one of the main weeds invading Chinese canola fields. The P. fugax resistant population SC-R, which survived quizalofop-p-ethyl at the field-recommended rate (67.5 g ha-1 ), was collected from a canola field in Qingsheng County in China. The present study aimed to (1) characterize the SC-R resistance pattern to acetyl-CoA carboxylase (ACCase)-inhibiting herbicides, and (2) investigate the mechanism of quizalofop-p-ethyl resistance in this population. RESULTS: Dose-response studies showed that resistance to quizalofop-p-ethyl and haloxyfop occurred in the SC-R population. Four transcripts/genes encoding the plastidic ACCase carboxyl-transferase domain were isolated from the P. fugax plants. No mutations in the four ACCase genes were detected in the SC-R population compared to the SC-S population. Pre-treatment with the known glutathione S-transferase (GST) inhibitor 4-chloro-7-nitrobenzoxadiazole (NBDCl), reversed resistance to quizalofop-p-ethyl and partially reversed resistance to haloxyfop-R-methyl in the resistant population (SC-R). However, the cytochrome P450 inhibitor malathion did not reverse the resistance. There was no difference in basal GST activity (using CDNB as a substrate), but there was higher inducible GST activity in SC-R relative to SC-S. Two GST genes, GST2c and GSTL3, were constitutively overexpressed in the resistant SC-R population. CONCLUSION: This study confirmed that resistance to quizalofop-p-ethyl in the resistant P. fugax population is likely nontarget-site based involving GST, and this resistance mechanism also partially confers haloxyfop-R-methyl resistance. © 2020 Society of Chemical Industry.


Assuntos
Resistência a Herbicidas , Acetil-CoA Carboxilase/genética , China , Glutationa Transferase/genética , Resistência a Herbicidas/genética , Herbicidas/farmacologia , Proteínas de Plantas/genética , Propionatos , Quinoxalinas
3.
J Food Sci ; 85(7): 2216-2226, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32579753

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is closely related to metabolic syndrome. We investigated the effect of a Psoralea corylifolia L. (PC) seeds extract (PCE) on NAFLD. PC seeds were extracted using different ethanol concentrations to produce five extracts, and the 70% ethanol PCE, which had the highest phenolic content, was used in subsequent in vitro and in vivo experiments. The inhibitory effect of PCE on hepatic steatosis was estimated using HepG2 cells treated with oleic acid (OA). In addition, an in vivo NAFLD model was established using high-fat diet (HFD)-induced obese C57BL/6 mice. Obesity was induced in mice over 14 weeks. PCE (100 or 200 mg/kg/day) was administered orally to mice after 8 weeks of the 14-week treatment period for 6 weeks. PCE suppressed lipid accumulation in OA-treated HepG2 cells. PCE ameliorated the antioxidant activity suppressions induced by the HFD. In addition, both PCE100 and PCE200 groups reduced lipid accumulation and the expression levels of inflammatory proteins as compared with HFD group. PCE administration significantly attenuated hepatic steatosis in liver tissues by decreasing the expression of lipogenic protein sterol regulatory element binding protein 1-c (SREBP-1c) and its downstream protein fatty acid synthase (FAS) in HFD-fed mice and in OA-treated HepG2 cells. Furthermore, PCE administration increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. These results suggest that PCE could be used as a functional material to prevent or ameliorate NAFLD by inhibiting lipid accumulation in liver. PRACTICAL APPLICATION: Psoralea corylifolia L. is rich in polyphenol and other phytochemicals. In this study, we identified the beneficial effects of Psoralea corylifolia L. extract on hepatic steatosis in oleic-acid-induced HepG2 cells and high-fat diet-fed mice. The result of this study will provide the evidence that a Psoralea corylifolia L. extract has potential use as a functional material for the prevention and amelioration of nonalcoholic fatty liver disease.


Assuntos
Ácidos Graxos não Esterificados/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Extratos Vegetais/administração & dosagem , Psoralea/química , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Células Hep G2 , Humanos , Lipogênese/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
4.
Am J Physiol Endocrinol Metab ; 319(1): E34-E42, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32228319

RESUMO

Nonalcoholic fatty liver disease (NAFLD) amplifies the risk of various liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis, and ultimately hepatocellular carcinoma. Accumulating evidence suggests the involvement of aberrant microRNAs (miRNAs or miRs) in the activation of cellular stress, inflammation, and fibrogenesis in hepatic cells at different stages of NAFLD and liver fibrosis. Here, we explored the potential role of miR-130b-5p in the pathogenesis of NAFLD, including lipid accumulation and insulin resistance, as well as the underlying mechanism. Initially, the expression of miR-130b-5p and insulin-like growth factor binding protein 2 (IGFBP2) was examined in the established high-fat diet-induced NAFLD mouse models. Then, the interaction between miR-130b-5p and IGFBP2 was validated using dual luciferase reporter assay. The effects of miR-130b-5p and IGFBP2 on lipid accumulation and insulin resistance, as well as the AKT pathway-related proteins, were evaluated using gain or loss-of-function approaches. miR-130b-5p was upregulated, and IGFBP2 was downregulated in liver tissues of NAFLD mice. miR-130b-5p targeted IGFBP2 and downregulated its expression. MiR-130b-5p inhibition or IGFBP2 overexpression reduced the expression of SREBP-1, LXRα, ChREBP, stearoyl CoA desaturase 1, acetyl CoA carboxylase 1, and fatty acid synthase, and levels of fasting blood glucose, fasting insulin, and homeostasis model assessment-insulin resistance, while increasing the ratio of p-AKT/AKT in NAFLD mice. Overall, downregulation of miR-130b-5p can prevent hepatic lipid accumulation and insulin resistance in NAFLD by activating IGFBP2-dependent AKT pathway, highlighting the potential use of anti-miR-130b-5p as therapeutic approaches for the prevention and treatment of NAFLD.


Assuntos
Dieta Hiperlipídica , Resistência à Insulina/genética , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Fígado/metabolismo , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/genética , Acetil-CoA Carboxilase/genética , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Glicemia/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Ácido Graxo Sintase Tipo I/genética , Expressão Gênica , Regulação da Expressão Gênica , Insulina/metabolismo , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Metabolismo dos Lipídeos/genética , Receptores X do Fígado/genética , Camundongos , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Estearoil-CoA Dessaturase/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/genética
5.
J Med Food ; 23(3): 312-318, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32191579

RESUMO

The aim of this study was to investigate the efficacy of an ethanol extract of Physalis alkekengi (PA) and its mechanistic pathway of action at the molecular level for its antiobesity properties. Four-week old male Institute of Cancer Research (ICR) mice were acclimatized for a week before starting the high-fat diet (HFD) for 2 weeks to induce obesity, followed by 8 more weeks of oral administration of 10 mg/kg orlistat and 300 mg/kg of PA extract, along with HFD. Body weights of the mice and feed and water intake were recorded weekly. After a total of 12 weeks, mice were euthanized, and blood, liver, and adipose tissues were harvested for further analysis. Administration of PA extract inhibited the progression of obesity by reducing weight gain, weight of adipose tissue, and normalizing serum triglyceride, glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase. PA extract prevented the progression of nonalcoholic steatohepatitis induced by HFD and prevented the enlargement of liver. Phosphorylation of adenosine monophosphate-activated protein kinase α increased while phosphorylation of acetyl-CoA carboxylase was reduced. The browning gene uncoupling protein 1 expression was also increased by PA extract treatment. Our findings revealed that the antiobesity properties of PA extract may be mediated by browning of white adipose tissue.


Assuntos
Tecido Adiposo Branco/metabolismo , Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Physalis/química , Extratos Vegetais/administração & dosagem , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Branco/efeitos dos fármacos , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Obesidade/genética , Obesidade/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
6.
Nat Cell Biol ; 22(2): 225-234, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32029897

RESUMO

Energy stress depletes ATP and induces cell death. Here we identify an unexpected inhibitory role of energy stress on ferroptosis, a form of regulated cell death induced by iron-dependent lipid peroxidation. We found that ferroptotic cell death and lipid peroxidation can be inhibited by treatments that induce or mimic energy stress. Inactivation of AMP-activated protein kinase (AMPK), a sensor of cellular energy status, largely abolishes the protective effects of energy stress on ferroptosis in vitro and on ferroptosis-associated renal ischaemia-reperfusion injury in vivo. Cancer cells with high basal AMPK activation are resistant to ferroptosis and AMPK inactivation sensitizes these cells to ferroptosis. Functional and lipidomic analyses further link AMPK regulation of ferroptosis to AMPK-mediated phosphorylation of acetyl-CoA carboxylase and polyunsaturated fatty acid biosynthesis. Our study demonstrates that energy stress inhibits ferroptosis partly through AMPK and reveals an unexpected coupling between ferroptosis and AMPK-mediated energy-stress signalling.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Acetil-CoA Carboxilase/genética , Ferroptose/genética , Rim/enzimologia , Peroxidação de Lipídeos/genética , Traumatismo por Reperfusão/genética , Células A549 , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Animais , Linhagem Celular Tumoral , Cicloexilaminas/farmacologia , Embrião de Mamíferos , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Ácidos Graxos Insaturados/biossíntese , Ferroptose/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Glucose/deficiência , Glucose/farmacologia , Humanos , Ferro/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Células MCF-7 , Camundongos , Camundongos Transgênicos , Fenilenodiaminas/farmacologia , Fosforilação , Piperazinas/antagonistas & inibidores , Piperazinas/farmacologia , Cultura Primária de Células , Pirazóis/farmacologia , Pirimidinas/farmacologia , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética
7.
Int J Mol Sci ; 21(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046209

RESUMO

Transgenic technology has huge application potential in agriculture and medical fields, such as producing new livestock varieties with new valuable features and xenotransplantation. However, how an exogenous gene affects the host animal's gene regulation networks and their health status is still poorly understood. In the current study, Fat-1 transgenic sheep were generated, and the tissues from 100-day abnormal (DAF_1) and normal (DAF_2) fetuses, postnatal lambs (DAF_4), transgenic-silencing (DAFG5), and -expressing (DAFG6) skin cells were collected and subjected to transcriptome sequencing, and their gene expression profiles were compared in multiple dimensions. The results were as follows. For DAF_1, its abnormal development was caused by pathogen invasion but not the introduction of the Fat-1 gene. Fat-1 expression down-regulated the genes related to the cell cycle; the NF-κB signaling pathway and the PI3K/Akt signaling pathway were down-regulated, and the PUFAs (polyunsaturated fatty acids) biosynthesis pathway was shifted toward the biosynthesis of high-level n-3 LC-PUFAs (long-chain PUFAs). Four key node genes, FADS2, PPARA, PRKACA, and ACACA, were found to be responsible for the gene expression profile shift from the Fat-1 transgenic 100-day fetus to postnatal lamb, and FADS2 may play a key role in the accumulation of n-3 LC-PUFAs in Fat-1 transgenic sheep muscle. Our study provides new insights into the FUFAs synthesis regulation in Fat-1 transgenic animals.


Assuntos
Animais Geneticamente Modificados/genética , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Insaturados/biossíntese , Ovinos/genética , Transcriptoma , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Células Cultivadas , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/genética , Subunidades Catalíticas da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Ácidos Graxos Insaturados/genética , NF-kappa B/genética , NF-kappa B/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
8.
J Pharmacol Exp Ther ; 372(3): 256-263, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900320

RESUMO

Excess intramyocellular lipid (IMCL) deposition in skeletal muscle is closely associated with insulin resistance. Pharmacological inhibition of acetyl-CoA carboxylase (ACC) 2 offers a promising approach to treat insulin resistance through stimulation of mitochondrial fatty acid oxidation (FAO) and reduction of IMCL deposition. Previously reported experimental ACC2 inhibitors exhibited plasma glucose-lowering effects in diabetic rodents. However, their antidiabetic action may be potentially biased by off-target effects on triglyceride metabolism or by neurologic side effects. In this study, we investigated a safety profile, target dependency of its action, and antidiabetic efficacy of compound 2e, a novel olefin derivative potent ACC2 selective inhibitor. Four-day administration of suprapharmacological dose of compound 2e did not exhibit any obvious side effects in Sprague-Dawley rats. In db/db mice, single administration of compound 2e led to significantly elevated FAO and reduced IMCL deposition in skeletal muscle. In ACC2 knockout mice, treatment with pharmacological doses of compound 2e did not reduce plasma triglyceride levels, whereas A-908292, a previously reported ACC2 inhibitor, caused a significant triglyceride reduction, showing that compound 2e was devoid of off-target triglyceride-lowering activity. Chronic treatment of db/db mice with compound 2e improved hyperglycemia but did not decrease plasma triglyceride levels. Additionally, compound 2e showed significant improvements of whole-body insulin resistance in the clamp study and insulin tolerance test. Collectively, compound 2e demonstrated a good safety profile and significant antidiabetic effects through inhibition of ACC2-dependent pathways. These findings provide further evidence that selective inhibition of ACC2 is an attractive strategy against insulin resistance and type 2 diabetes. SIGNIFICANCE STATEMENT: This study shows that pharmacological inhibition of acetyl-CoA carboxylase (ACC) 2 leads to significant improvements in whole-body glucose homeostasis, independently of off-target metabolic pathways and toxicity, which were observed in previously reported ACC2 inhibitors. These findings support the concept that ACC2-selective inhibitors will be a novel remedy for treatment of type 2 diabetes.


Assuntos
Acetil-CoA Carboxilase/antagonistas & inibidores , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemiantes/uso terapêutico , Resistência à Insulina , Acetil-CoA Carboxilase/genética , Animais , Glicemia/análise , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/farmacologia , Hipoglicemiantes/toxicidade , Insulina/metabolismo , Camundongos Knockout , Músculo Esquelético/enzimologia , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Ratos Sprague-Dawley , Testes de Toxicidade , Triglicerídeos/sangue
9.
PLoS One ; 15(1): e0227666, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945099

RESUMO

Species-specific sex pheromones play key roles in moth sexual communication. Although the general pathway of Type-I sex pheromone biosynthesis is well established, only a handful of genes encoding enzymes involved in this pathway have been characterized. Streltzoviella insularis is a destructive wood-boring pest of many street trees in China, and the female sex pheromone of this species comprises a blend of (Z)-3-tetradecenyl acetate, (E)-3-tetradecenyl acetate, and (Z)-5-dodecenyl acetate. This organism therefore provides an excellent model for research on the diversity of genes and molecular mechanisms involved in pheromone production. Herein, we assembled the pheromone gland transcriptome of S. insularis by next-generation sequencing and identified 74 genes encoding candidate key enzymes involved in the fatty acid biosynthesis, ß-oxidation, and functional group modification. In addition, tissue expression patterns further showed that an acetyl-CoA carboxylase and two desaturases were highly expressed in the pheromone glands compared with the other tissues, indicating possible roles in S. insularis sex pheromone biosynthesis. Finally, we proposed putative S. insularis biosynthetic pathways for sex pheromone components and highlighted candidate genes. Our findings lay a solid foundation for understanding the molecular mechanisms underpinning S. insularis sex pheromone biosynthesis, and provide potential targets for disrupting chemical communication that could assist the development of novel pest control methods.


Assuntos
Genes de Insetos , Mariposas/genética , Mariposas/metabolismo , Atrativos Sexuais/biossíntese , Atrativos Sexuais/genética , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Acetiltransferases/genética , Acetiltransferases/metabolismo , Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/metabolismo , Aldeído Redutase/genética , Aldeído Redutase/metabolismo , Animais , Vias Biossintéticas/genética , China , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Filogenia , Receptores de Neuropeptídeos/genética , Receptores de Neuropeptídeos/metabolismo , Glândulas Odoríferas/metabolismo , Análise de Sequência de RNA , Transcriptoma
10.
Appl Microbiol Biotechnol ; 104(4): 1647-1660, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31853567

RESUMO

More than two-third of known antibiotics are produced by actinomycetes of the genus Streptomyces. Unfortunately, the production rate from Streptomyces natural antibiotic is extremely slow and thus cannot satisfy industrial demand. In this study, the production of antibiotics by Streptomyces is enhanced by a "superplasmid" which including global regulatory factors afsR, cyclic adenosine receptor protein (CRP), RNA polymerase beta subunits (rpoB) with point mutation and acetyl coenzyme A carboxylase gene (accA2BE), these elements are controlled by the PermE* promoter and then transfer into Streptomyces coelicolor M145, Streptomyces mutabilis TRM45540, Streptomyces hygroscopicus XM201, and Streptomyces hygroscopicus ATCC29253 by conjugation to generate exconjugants. NMR, HPLC, and LC-MS analyses revealed that the superplasmid led to the overproduction of actinorhodin (101.90%), undecylprodigiosin (181.60%) in S. coelicolor M145:: pLQ003, of rapamycin (110%), hygrocin A (163.4%) in S. hygroscopicus ATCC29253:: pLQ003, and of actinomycin D (11.78%) in S. mutabilis TRM45540:: pLQ003, and also to the downregulation of geldanamycin in S. hygroscopicus XM201, but we found that mutant strains in mutant strains of S. hygroscopicus XM201 with regulatory factors inserted showed several peaks that were not found in wild-type strains. The results of the present work indicated that the regulator net working in Streptomyces was not uniform, the superplasmid we constructed possibly caused this overproduction and downregulation in different Streptomyces.


Assuntos
Antibacterianos/biossíntese , Engenharia Genética/métodos , Plasmídeos/genética , Streptomyces/genética , Acetil-CoA Carboxilase/genética , Bactérias/efeitos dos fármacos , Benzoquinonas/metabolismo , Dactinomicina/biossíntese , Lactamas Macrocíclicas/metabolismo , Mutação Puntual , Regiões Promotoras Genéticas
11.
Biochem Biophys Res Commun ; 523(2): 429-433, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-31870547

RESUMO

Polyamines are low molecular weight, organic cations that play a critical role in many major cellular processes including cell cycle regulation and apoptosis, cellular division, tissue proliferation, and cellular differentiation; however, the functions of polyamines in regulating the storage of metabolic fuels such as triglycerides and glycogen is poorly understood. To address this question, we focused on the Drosophila homolog of ornithine decarboxylase (Odc1), the first rate-limiting enzyme in the synthesis of polyamines. Mutants in Odc1 are lethal, but heterozygotes were viable to adulthood. Odc1 heterozygotes appeared larger than their genetic background control flies and consistent with this observation, weighed more than the controls. However, the increased weight was not due to increased food consumption as heterozygotes ate less than the controls. Interestingly, Odc1 heterozygous flies had augmented triglyceride storage, and this lipid phenotype was due to increased triglyceride storage per cell and an increase in the number of fat cells produced. Odc1 heterozygous flies also displayed increased expression of the lipid synthesis genes fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), suggesting increased lipid synthesis was the cause of the augmented triglyceride phenotype. These results provide a link between the expression of Odc1 and triglyceride storage suggesting that the polyamine pathway plays a role in regulating lipid metabolism.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Ornitina Descarboxilase/genética , Triglicerídeos/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Ácidos Graxos/genética , Ácidos Graxos/metabolismo , Feminino , Regulação da Expressão Gênica , Heterozigoto , Mutação , Ornitina Descarboxilase/metabolismo , Triglicerídeos/genética
12.
Lipids Health Dis ; 18(1): 211, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805951

RESUMO

BACKGROUND: Insulin resistance (IR) and lipid peroxidation are accepted as 'two-hit' hypothesis of Non-alcoholic fatty liver disease (NAFLD). However, there are few published research on identifying genes which connect lipid and glucose metabolism by gene microarray. OBJECTIVE: To identify target genes related to lipid and glucose metabolism that might be responsible for the pathogenesis of NAFLD. METHODS: A rat model of NAFLD was established by feeding male rats with high-fat diet and gene expression profiles of liver tissues were determined using Agilent DNA microarray. We then investigated differentially expressed genes (DEGs) and intersection of them by using Gene Ontology (GO) and Pathway Analyses. Target genes were verified by Real-time polymerase chain reaction (RT-PCR). RESULTS: Compared with control, 932 genes, including 783 up-regulated and 149 down-regulated, exhibited differences in expression. The up-regulated genes were involved in biosynthesis, cell development, cell differentiation and down-regulated genes contributed to biological metabolic process, adipokine metabolic pathway and insulin signaling pathway. We identified genes involved in insulin signaling pathway, Notch signaling pathway and lipid synthetic process to be closely related to liver fat accumulation and insulin resistance. Among them, IGFBP7, Notch1 and HMGCR were up-regulated (2.85-fold, 3.22-fold, and 2.06-fold, respectively, all P < 0.05) and ACACB was down-regulated (2.08-fold, P < 0.01). These four genes supposed to connect lipid and glucose metabolism after GO and Pathway analyses. CONCLUSIONS: These findings provide innovative information on the whole genome expression profile due to high-fat diet feeding, and bring new insight into the regulating effects of genes on the lipid and glucose metabolism of NAFLD.


Assuntos
Acetil-CoA Carboxilase/genética , Glucose/metabolismo , Hidroximetilglutaril-CoA Redutases/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Receptor Notch1/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Metabolismo dos Carboidratos/genética , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Resistência à Insulina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Metabolismo dos Lipídeos/genética , Fígado/patologia , Masculino , Análise em Microsséries , Anotação de Sequência Molecular , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Ratos , Ratos Sprague-Dawley , Receptor Notch1/metabolismo , Transdução de Sinais
13.
Elife ; 82019 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-31742554

RESUMO

Because old age is the greatest risk factor for dementia, a successful therapy will require an understanding of the physiological changes that occur in the brain with aging. Here, two structurally distinct Alzheimer's disease (AD) drug candidates, CMS121 and J147, were used to identify a unique molecular pathway that is shared between the aging brain and AD. CMS121 and J147 reduced cognitive decline as well as metabolic and transcriptional markers of aging in the brain when administered to rapidly aging SAMP8 mice. Both compounds preserved mitochondrial homeostasis by regulating acetyl-coenzyme A (acetyl-CoA) metabolism. CMS121 and J147 increased the levels of acetyl-CoA in cell culture and mice via the inhibition of acetyl-CoA carboxylase 1 (ACC1), resulting in neuroprotection and increased acetylation of histone H3K9 in SAMP8 mice, a site linked to memory enhancement. These data show that targeting specific metabolic aspects of the aging brain could result in treatments for dementia.


Assuntos
Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Mitocôndrias/metabolismo , Acetilcoenzima A/efeitos dos fármacos , Acetilcoenzima A/metabolismo , Acetil-CoA Carboxilase/genética , Acetilação/efeitos dos fármacos , Envelhecimento/patologia , Doença de Alzheimer/fisiopatologia , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Curcumina/análogos & derivados , Curcumina/farmacologia , Humanos , Memória/efeitos dos fármacos , Memória/fisiologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
14.
Appl Microbiol Biotechnol ; 103(23-24): 9593-9606, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31713669

RESUMO

FK520 (ascomycin), a 23-membered macrolide with immunosuppressive activity, is produced by Streptomyces hygroscopicus. The problem of low yield and high impurities (mainly FK523) limits the industrialized production of FK520. In this study, the FK520 yield was significantly improved by strain mutagenesis and genetic engineering. First, a FK520 high-producing strain SFK-6-33 (2432.2 mg/L) was obtained from SFK-36 (1588.4 mg/L) through ultraviolet radiation mutation coupled with streptomycin resistance screening. The endogenous crotonyl-CoA carboxylase/reductase (FkbS) was found to play an important role in FK520 biosynthesis, identified with CRISPR/dCas9 inhibition system. FkbS was overexpressed in SFK-6-33 to obtain the engineered strain SFK-OfkbS, which produced 2817.0 mg/L of FK520 resulting from an increase in intracellular ethylmalonyl-CoA levels. In addition, the FK520 levels could be further increased with supplementation of crotonic acid in SFK-OfkbS. Overexpression of acetyl-CoA carboxylase (ACCase), used for the synthesis of malonyl-CoA, was also investigated in SFK-6-33, which improved the FK520 yield to 3320.1 mg/L but showed no significant inhibition in FK523 production. To further enhance FK520 production, FkbS and ACCase combinatorial overexpression strain SFK-OASN was constructed; the FK520 production increased by 44.4% to 3511.4 mg/L, and the FK523/FK520 ratio was reduced from 9.6 to 5.6% compared with that in SFK-6-33. Finally, a fed-batch culture was carried out in a 5-L fermenter, and the FK520 yield reached 3913.9 mg/L at 168 h by feeding glycerol, representing the highest FK520 yield reported thus far. These results demonstrated that traditional mutagenesis combined with metabolic engineering was an effective strategy to improve FK520 production.


Assuntos
Engenharia Metabólica/métodos , Streptomyces/genética , Streptomyces/metabolismo , Tacrolimo/análogos & derivados , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Acil Coenzima A/metabolismo , Acil-CoA Desidrogenases/genética , Acil-CoA Desidrogenases/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Sistemas CRISPR-Cas , Crotonatos/metabolismo , Expressão Gênica , Imunossupressores/metabolismo , Mutagênese , Tacrolimo/metabolismo , Raios Ultravioleta
15.
Lipids Health Dis ; 18(1): 191, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684957

RESUMO

BACKGROUND: Steatosis is an important clinical manifestation associated with chronic hepatitis C virus (HCV) infection. AMP-activated protein kinase (AMPK), a major mediator of lipid metabolism, regulates HCV-associated hepatic steatosis, but the underlying mechanisms remain obscure. Here we investigated the mechanism of HCV nonstructural protein 5A (NS5A)-induced lipid accumulation by the AMPK/SREBP-1c pathway. METHODS: We generated model mice by injecting recombinant lentiviral particles expressing the NS5A protein (genotype 3a) via the tail vein. The serum levels of alanine aminotransferase (ALT), free fatty acids (FFAs) and triglycerides (TG) were examined. H&E and Oil Red O staining were used to examine lipid droplets. Immunohistochemistry staining, quantitative real-time PCR and Western blotting were used to determine the expression of lipogenic genes. RESULTS: Our results showed that the serum levels of ALT, FFAs and TG, as well as the accumulation of hepatic lipid droplets, were increased significantly in mice infected with NS5A-expressing lentiviral particles. NS5A inhibited AMPK phosphorylation and increased the expression levels of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase 1 (ACC1) and fatty acid synthase (FASN) in vivo and in vitro. Further investigation revealed that pharmacological activation or ectopic expression of AMPK neutralized the upregulation of SREBP-1c, ACC1 and FASN, and ameliorated hepatic lipid accumulation induced by NS5A. Ectopic expression of SREBP-1c enhanced NS5A-induced hepatic lipid accumulation, which was dramatically reversed by pharmacological activation of AMPK. CONCLUSIONS: Collectively, we demonstrate that NS5A induces hepatic lipid accumulation via the AMPK/SREBP-1c pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteínas não Estruturais Virais/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Western Blotting , Linhagem Celular , Feminino , Células Hep G2 , Humanos , Imuno-Histoquímica , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase em Tempo Real , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteínas não Estruturais Virais/genética
16.
J Agric Food Chem ; 67(45): 12419-12427, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31610126

RESUMO

The liver X receptors (LXRs) are major regulators of lipogenesis, and their reduced activation by an inhibitor could be a treatment strategy for fatty liver disease. Small molecules originating from dietary food are considered suitable and attractive drug candidates for humans in terms of safety. In this study, an edible plant, Lysimachia vulgaris (LV), used as a traditional and medicinal food in East Asia was evaluated for lipogenesis decreasing effects. Activity-guided fractionation was performed, and the isolated compounds were identified using spectroscopic methods. We conducted in vitro real-time polymerase chain reaction (PCR) and Western blotting as well as histological and biochemical analyses following in vivo treatments. Using a high-fat diet animal model, we confirmed that LV extracts (LVE) decreased lipogenic metabolism and restored liver function to control levels. To identify active components, we conducted activity-guided fractionation and then isolated compounds. Two compounds, loliolide and pinoresinol, were identified in the dichloromethane fraction, and they significantly attenuated the expression levels of lipogenic factors including sterol regulatory element-binding protein (SREBP)-1, stearoyl-CoA desaturase 1 (SCD1), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). Importantly, loliolide and pinoresinol significantly accelerated the protein degradation of LXRs by enhanced ubiquitination, which inhibited lipogenesis. These results suggest that loliolide and pinoresinol might be potential candidate supplementary treatments for nonalcoholic fatty liver disease (NAFLD) by reducing lipogenesis through increased ubiquitination of LXRs.


Assuntos
Benzofuranos/administração & dosagem , Furanos/administração & dosagem , Lignanas/administração & dosagem , Lipogênese/efeitos dos fármacos , Receptores X do Fígado/metabolismo , Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Primulaceae/química , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Ácido Graxo Sintases/genética , Ácido Graxo Sintases/metabolismo , Humanos , Fígado/metabolismo , Receptores X do Fígado/genética , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Triglicerídeos/metabolismo
17.
Lipids Health Dis ; 18(1): 168, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477154

RESUMO

BACKGROUND: The alteration of lipid metabolism in cancer cells is recognized as one of the most important metabolic hallmarks of cancer. Membrane rafts defined as plasma membrane microdomains enriched in cholesterol and sphingolipids serve as platforms for signaling regulation in cancer. The main purpose of this study was to evaluate the effect of the cholesterol metabolite, 4-cholesten-3-one, on lipid metabolism and membrane raft integrity in two breast cancer cell lines, MCF-7 and MDA-MB-231. Its ability to reduce cell viability and migration has also been investigated. METHODS: RT-qPCR was performed to evaluate the expression of enzymes involved in lipogenesis and cholesterol synthesis, and ABCG1 and ABCA1 transporters involved in cholesterol efflux. Its effect on cell viability and migration was studied using the MTT assay, the wound healing assay and the Transwell migration assay, respectively. The effect of 4-cholesten-3-one on membrane rafts integrity was investigated by studying the protein expression of flotillin-2, a membrane raft marker, and raft-enriched EGFR by western blot. RESULTS: Interestingly, we found that 4-cholesten-3-one treatment decreased mRNA expression of different enzymes including ACC1, FASN, SCD1 and HMGCR. We further demonstrated that 4-cholesten-3-one increased the expression of ABCG1 and ABCA1. We also found that 4-cholesten-3-one decreased the viability of MCF-7 and MDA-MB-231 cells. This effect was neutralized after treatment with LXR inverse agonist or after LXRß knockdown by siRNA. As a result, we also demonstrated that 4-cholesten-3-one disrupts membrane rafts and cell migration capacity. CONCLUSION: Our results show that 4-cholesten-3-one exerts promising antitumor activity by altering LXR-dependent lipid metabolism in breast cancer cells without increasing lipogenesis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Colestenonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Receptores X do Fígado/genética , Microdomínios da Membrana/efeitos dos fármacos , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Receptores ErbB/genética , Receptores ErbB/metabolismo , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , Lipogênese/genética , Receptores X do Fígado/metabolismo , Células MCF-7 , Microdomínios da Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transdução de Sinais , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Células THP-1
18.
BMC Complement Altern Med ; 19(1): 255, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519174

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is characterized by excessive hepatic lipid accumulation. Many studies have suggested that lipid overload is the key initial factor that contributes to hepatic steatosis. Our previous study indicated that diosgenin (DSG) has a beneficial effect on energy metabolism, but the underlying mechanism remains unclear. METHODS: Human normal hepatocytes (LO2 cells) were incubated with palmitic acid to establish the cell model of nonalcoholic fatty liver. The effects of DSG on lipid metabolism, glucose uptake and mitochondrial function were evaluated. Furthermore, the mechanism of DSG on oxidative stress, lipid consumption and lipid synthesis in LO2 cells was investigated. RESULTS: The results indicated that palmitic acid induced obvious lipid accumulation in LO2 cells and that DSG treatment significantly reduced the intracellular lipid content. DSG treatment upregulated expression of lipolysis proteins, including phospho-AMP activated protein kinase (p-AMPK), phospho-acetyl-coA carboxylase (p-ACC) and carnitine acyl transferase 1A (CPT-1A), and inhibited expression of lipid synthesis-related proteins, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Additionally, DSG-treated cells displayed a marked improvement in mitochondrial function, with less production of reactive oxygen species and a higher mitochondrial membrane potential compared with the model group. CONCLUSION: This study suggests that DSG can reduce intracellular lipid accumulation in LO2 cells and that the underlying mechanism may be related to the improving oxidative stress, increasing fatty acid ß-oxidation and decreasing lipid synthesis. The above changes might be mediated by the activation of the AMPK/ACC/CPT-1A pathway and inhibition of the SREBP-1c/FAS pathway.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Diosgenina/farmacologia , Ácido Graxo Sintases/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Ácido Palmítico/efeitos adversos , Proteínas Quinases Ativadas por AMP/genética , Acetil-CoA Carboxilase/genética , Carnitina O-Acetiltransferase/genética , Carnitina O-Acetiltransferase/metabolismo , Linhagem Celular , Ácido Graxo Sintases/genética , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/genética , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo
19.
Mol Biol Rep ; 46(6): 6271-6276, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31522344

RESUMO

Herbicides inhibiting acetyl-coenzyme A carboxylase (ACCase) are very effective in controlling grass weeds including weedy-rice in paddy rice production systems. The ACCase inhibitor affects the enzyme by blocking fatty acid biosynthesis resulting in plant death. The herbicide resistance in rice is conferred by a single point mutation with an amino acid substitution of the carboxyl transferase domain of the ACCase gene. An assay based on the tetra-primer ARMS-PCR method was developed to detect the SNP G2027T that causes a tryptophan-cysteine substitution in the gene encoding chloroplastic ACCase in rice. The protocol was tested in 453 rice samples from a segregant population for validation of the assay. This technique can be exploited to monitor resistant lines in rice breeding programs to detect homozygous or heterozygous resistant genotypes and homozygous susceptible genotypes. The presence of resistant ACCase allele(s) can be detected with rapidity, simplicity, at low cost and can be used in any molecular biology laboratory with minimal equipment.


Assuntos
Acetil-CoA Carboxilase/genética , Resistência a Herbicidas/genética , Oryza/efeitos dos fármacos , Oryza/genética , Proteínas de Plantas/genética , Acetil-CoA Carboxilase/metabolismo , Alelos , Substituição de Aminoácidos , Sequência de Bases , Catálise , Mutação , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Polimorfismo de Nucleotídeo Único
20.
Chemosphere ; 235: 1030-1040, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31561292

RESUMO

Organic pesticides are one of the main environmental pollutants, and how to reduce their environmental risks is an important issue. In this contribution, we disclose the molecular basis for the resistance of American sloughgrass to aryloxyphenoxypropionic acid pesticides using site-directed mutagenesis and molecular modeling and then construct an effective screening model. The results indicated that the target-site mutation (Trp-1999-Leu) in acetyl-coenzyme A carboxylase (ACCase) can affect the effectiveness of the pesticides (clodinafop, fenoxaprop, cyhalofop, and metamifop), and the plant resistance to fenoxaprop, clodinafop, cyhalofop, and metamifop was found to be 564, 19.5, 10, and 0.19 times, respectively. The established computational models (i.e. wild-type/mutant ACCase models) could be used for rational screening and evaluation of the resistance to pesticides. The resistance induced by target gene mutation can markedly reduce the bioreactivity of the ACCase-clodinafop/fenoxaprop adducts, and the magnitudes are 10 and 102, respectively. Such event will seriously aggravate environmental pollution. However, the biological issue has no distinct effect on cyhalofop (RI=10), and meanwhile it may markedly increase the bioefficacy of metamifop (RI=0.19). We could selectively adopt the two chemicals so as to decrease the residual pesticides in the environment. Significantly, research findings from the computational screening models were found to be negatively correlated with the resistance level derived from the bioassay testing, suggesting that the screening models can be used to guide the usage of pesticides. Obviously, this story may shed novel insight on the reduction of environmental risks of pesticides and other organic pollutants.


Assuntos
Acetil-CoA Carboxilase/antagonistas & inibidores , Biologia Computacional/métodos , Resistência a Herbicidas/genética , Praguicidas/toxicidade , Proteínas de Plantas/antagonistas & inibidores , Poaceae/crescimento & desenvolvimento , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Anilidas/toxicidade , Benzoxazóis/toxicidade , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Modelos Moleculares , Simulação de Acoplamento Molecular , Mutagênese Sítio-Dirigida , Mutação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/efeitos dos fármacos , Poaceae/enzimologia , Propionatos/toxicidade , Conformação Proteica , Piridinas/toxicidade , Estados Unidos
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