RESUMO
BACKGROUND: Chloris virgata is a troublesome weed in tropical regions. With the evolution of glyphosate resistance in key grass species, acetyl CoA carboxylase (ACCase) inhibitors have become a commonly used tool in soybean production areas in Brazil. We assessed if suspected resistant populations exhibited cross resistance to the different classes of ACCase inhibitors and investigated the resistance mechanisms in C. virgata. RESULTS: Dose-response experiments revealed resistance to haloxyfop-methyl and pinoxaden, with 432- and 3-fold resistance, respectively, compared to susceptible populations. Due to the lack of genetic resources for C. virgata, we sequenced, assembled, and annotated the genome using short-read Illumina technology. The k-mer analysis estimated a genome size of approximately 336 Mbp, with BUSCO completeness of 97%, and over 36 000 gene models were annotated. We examined if ACCase copy number variation and increased gene expression were involved in the resistance phenotype and found no difference when compared to a susceptible population. A mutation was detected in ACCase that encodes for amino acid position 2027, resulting in a tryptophan-to-cysteine (Trp2027Cys) substitution. We found the resistant population absorbed 11.4% less herbicide and retained 21% more herbicide on the treated leaf compared to the susceptible population. We developed a genotyping assay targeting the resistance-endowing Trp2027Cys substitution for quick resistance diagnosis. CONCLUSION: A Trp2027Cys amino acid substitution in ACCase confers resistance to haloxyfop and pinoxaden in C. virgata. We provide important insights into the evolutionary history of C. virgata and a draft genome as a useful resource to further our understanding of the biology in the genus Chloris. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Assuntos
Herbicidas , Herbicidas/farmacologia , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Variações do Número de Cópias de DNA , Resistência a Herbicidas/genética , Poaceae/genética , Mutação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
PURPOSE: The de novo lipogenesis has been a longstanding observation in hepatocellular carcinoma (HCC). However, the prognostic value and carcinogenic roles of the enzyme Acetyl-CoA carboxylase alpha (ACACA) in HCC remains unknown. METHODS: The proteins with remarkable prognostic significance were screened out from The Cancer Proteome Atlas Portal (TCPA) database. Furthermore, the expression characteristics and prognostic value of ACACA were evaluated in multiple databases and the local HCC cohort. The loss-of-function assays were performed to uncover the potential roles of ACACA in steering malignant behaviors of HCC cells. The underlying mechanisms were conjectured by bioinformatics and validated in HCC cell lines. RESULTS: ACACA was identified as a crucial factor of HCC prognosis. Bioinformatics analyses showed that HCC patients with higher expression of ACACA protein or mRNA levels had poor prognosis. Knockdown of ACACA remarkably crippled the proliferation, colony formation, migration, invasion, epithelial-mesenchymal transition (EMT) process of HCC cells and induced the cell cycle arrest. Mechanistically, ACACA might facilitate the malignant phenotypes of HCC through aberrant activation of Wnt/ß-catenin signaling pathway. In addition, ACACA expression was associated with the dilute infiltration of immune cells including plasmacytoid DC (pDC) and cytotoxic cells by utilization of relevant database analysis. CONCLUSION: ACACA could be a potential biomarker and molecular target for HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , beta Catenina/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Prognóstico , Proteínas/metabolismoRESUMO
There are doubts about the impact of non-nutritive sweeteners consumption on lipogenic and glycolytic metabolism. Therefore, the objective was to determine the effects of chronic consumption of sweeteners on the activity levels of the enzymes glucokinase (GK), phosphofructokinase-1 (PFK-1), pyruvate kinase (PKL), acetyl coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) in livers' extracts. Groups of male and female Wistar rats drank solutions of sweeteners for 480 days: Sucrose 10%, glucose 14%, fructose 7%, acesulfame K 0.05%, aspartame:acesulfame mixture 1.55%, sucralose 0.017%, saccharin 0.033%, and a control group. The enzymatic activity in livers' extracts was determined. Likewise, the levels of glucose, triglycerides, insulin, glucagon, and leptin were determined. In both genders, there were significant differences in the levels of enzymatic activity, hormonal, and biochemical parameters due to sweeteners consumption. The highest glycolytic and lipogenic enzyme activity levels were observed in the groups that ingested nutritive sweeteners and saccharin.
Assuntos
Adoçantes não Calóricos , Sacarina , Animais , Ratos , Feminino , Masculino , Sacarina/metabolismo , Aspartame , Adoçantes não Calóricos/farmacologia , Leptina , Adoçantes Calóricos , Glucoquinase/metabolismo , Acetil-CoA Carboxilase/metabolismo , Piruvato Quinase/metabolismo , Glucagon/metabolismo , Ratos Wistar , Edulcorantes/farmacologia , Sacarose , Glucose/metabolismo , Insulina/metabolismo , Frutose , Triglicerídeos/metabolismo , Fígado/metabolismo , Ácido Graxo Sintases/metabolismoRESUMO
Antenatal corticosteroid therapy is used to reduce neonatal mortality in preterm infants but it is currently unknown whether this intervention affects lipid metabolism at the peripartum. This study aimed to evaluate if antenatal corticosteroid therapy in pregnant rats and women affects lipid metabolism during early lactation. We evaluated women at risk of preterm delivery that received corticosteroid therapy (CASE) and women that were not exposed to corticosteroid and were not at risk of preterm delivery (CONTROL). Samples were collected to measure serum and milk triacylglycerol (TAG) three days after delivery. Rats were treated with dexamethasone (DEX) between the 15th and the 20th days of pregnancy. Samples were collected at different days after delivery (L3, L8 and L14). TAG was measured in serum, liver and mammary gland (MG). TAG appearance rates were measured after tyloxapol injection and gavage with olive oil. We also evaluated the expression of key genes related to lipid metabolism in the liver and in the MG and hepatic phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). CASE volunteers delivered earlier than CONTROL but presented unaltered milk and serum TAG concentrations. Early lactating DEX rats exhibited increased TAG in serum, MG and milk. No changes in CD36 and LPL were detected in the MG and liver. Early lactating DEX rats displayed increased TAG appearance rate and reduced hepatic AMPK/ACC phosphorylation. Our data revealed that antenatal corticosteroid therapy reduces hepatic AMPK/ACC phosphorylation during early lactation that reflects in increased TAG concentration in serum, MG and milk.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Corticosteroides/uso terapêutico , Lactação/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Acetil-CoA Carboxilase/metabolismo , Adulto , Animais , Dexametasona/farmacologia , Feminino , Expressão Gênica , Humanos , Fígado/metabolismo , Masculino , Glândulas Mamárias Animais/metabolismo , Leite Humano/química , Trabalho de Parto Prematuro/prevenção & controle , Fosforilação , Gravidez , Ratos , Ratos Wistar , Triglicerídeos/sangue , Triglicerídeos/metabolismo , Adulto JovemRESUMO
The occurrence of multiple herbicide resistant weeds has increased considerably in glyphosate-resistant soybean fields in Brazil; however, the mechanisms governing this resistance have not been studied. In its study, the target-site and nontarget-site mechanisms were characterized in an Eleusine indica population (R-15) with multiple resistance to the acetyl-CoA carboxylase (ACCase) inhibitors, glyphosate, imazamox, and paraquat. Absorption and translocation rates of 14C-diclofop-methyl14C-imazamox and 14C-glyphosate of the R-15 population were similar to those of a susceptible (S-15) population; however, the R-15 population translocated â¼38% less 14C-paraquat to the rest of plant and roots than the S-15 population. Furthermore, the R-15 plants metabolized (by P450 cytochrome) 55% and 88% more diclofop-methyl (conjugate) and imazamox (imazamox-OH and conjugate), respectively, than the S-15 plants. In addition, the Pro-106-Ser mutation was found in the EPSPS gene of this population. This report describes the first characterization of the resistance mechanisms in a multiple herbicide resistant weed from Brazil.
Assuntos
Eleusine/efeitos dos fármacos , Glicina/análogos & derivados , Resistência a Herbicidas , Herbicidas/farmacologia , Acetil-CoA Carboxilase/antagonistas & inibidores , Acetil-CoA Carboxilase/genética , Acetil-CoA Carboxilase/metabolismo , Brasil , Eleusine/enzimologia , Eleusine/genética , Inibidores Enzimáticos/farmacologia , Glicina/farmacologia , Imidazóis/farmacologia , Paraquat/farmacologia , Proteínas de Plantas/antagonistas & inibidores , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , GlifosatoRESUMO
Malaria is a major parasitic disease of humans and is a health public problem that affects more than 100 countries. In 2017, it caused nearly half a million deaths out of 219 million infections. Malaria is caused by the protozoan parasites of the genus Plasmodium and is transmitted by female mosquitoes of the genus Anopheles. Once in the bloodstream, Plasmodium merozoites invade erythrocytes and proliferate until the cells lyses and release new parasites that invade other erythrocytes. Remarkably, they can manipulate the vertebrate host's lipid metabolism pathways, since they cannot synthesize lipid classes that are essential for their development and replication. In this study, we show that mice infected with Plasmodium chabaudi present a completely different plasma profile from control mice, with marked hyperproteinemia, hypertriglyceridemia, hypoglycemia, and hypocholesterolemia. In addition, white adipose and hepatic tissue and analyses from infected animals revealed the accumulation of triacylglycerol in both tissues and free fatty acids and free cholesterol in the liver. Hepatic mRNA and protein expression of key enzymes and transcription factors involved in lipid metabolism were also altered by P. chabaudi infection, leading to a lipogenic state. The enzyme 5' AMP-activated protein kinase (AMPK), a master regulator of cell energetic metabolism, was also modulated by the parasite, which reduced AMPK phosphorylation levels upon infection. Pretreatment with metformin for 21 days followed by infection with P. chabaudi was effective in preventing infection of mice and also lowered the hepatic accumulation of lipids while activating AMPK. Together, these results provide new and important information on the specific molecular mechanisms induced by the malaria parasite to regulate hepatic lipid metabolism in order to facilitate its development, proliferation, and lifespan in its vertebrate host.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Acetil-CoA Carboxilase/metabolismo , Colesterol/metabolismo , Dislipidemias/etiologia , Ácidos Graxos não Esterificados/metabolismo , Fígado/metabolismo , Malária/complicações , Plasmodium chabaudi/metabolismo , Triglicerídeos/metabolismo , Animais , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Fígado/parasitologia , Malária/tratamento farmacológico , Malária/metabolismo , Malária/parasitologia , Masculino , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Resultado do TratamentoRESUMO
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 ÚnicoRESUMO
The committed and rate-limiting step in fatty acid biosynthesis is catalyzed by acetyl-CoA carboxylase (ACC). In previous studies we showed that ACC activity is inhibited through interactions with the PII signaling proteins in vitro. Here we provide in vivo support for that model; we noted that PII proteins are able to reduce malonyl-CoA levels in vivo in Escherichia coli. Furthermore, we show that fatty acid biosynthesis is strongly enhanced in E. coli strains carrying deletions in PII coding genes. Given that PII proteins act as conserved negative regulators of ACC in Bacteria, our findings may be explored to engineer other prokaryotes to improve fatty acid yields, thereby turning microbial biofuel production economically competitive in the future.
Assuntos
Proteínas de Escherichia coli/genética , Escherichia coli/metabolismo , Ácidos Graxos/biossíntese , Acetil-CoA Carboxilase/metabolismo , Biocombustíveis , Escherichia coli/genética , Deleção de Genes , Transdução de SinaisRESUMO
Several studies have shown that pharmacological concentrations of biotin decrease serum lipid concentrations and the expression of lipogenic genes. Previous studies on epididymal adipose tissue in mice revealed that 8 weeks of dietary biotin supplementation increased the protein abundance of the active form of AMPK and the inactive forms acetyl CoA carboxylase (ACC)-1 and - 2, and decreased serum free fatty acid concentrations but did not affect lipolysis. These data suggest that pharmacological concentrations of the vitamin might affect fatty acid metabolism. In this work, we investigated the effects of pharmacological biotin concentrations on fatty acid synthesis, oxidation, and uptake in 3T3-L1 adipocytes. Similar to observations in mice, biotin-supplemented 3T3-L1 adipose cells increased the protein abundance of active T172 -AMPK and inactive ACC-1 and -2 forms. No changes were observed in the expression of the transcriptional factor PPARα and carnitine-palmitoyltransferase-1 (CPT-1). Radiolabeled assays indicated a decrease in fatty acid synthesis; an increase in fatty acid oxidation and fatty acid incorporation rate into the lipid fraction between control cells and biotin-supplemented cells. The data revealed an increase in the mRNA abundance of the fatty acid transport proteins Fatp1 and Acsl1 but not Cd36 or Fatp4 mRNA. Furthermore, the abundance of glycerol phosphate acyl transferase-3 protein was increased. Triglyceride content was not affected. Lipid droplet numbers showed an increase and their areas were smaller in the biotin-supplemented group. In conclusion, these data indicate that biotin supplementation causes a decrease in fatty acid synthesis and an increase in its oxidation and uptake. © 2018 BioFactors, 45(2):259-270, 2019.
Assuntos
Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Biotina/farmacologia , Ácidos Graxos/metabolismo , Células 3T3-L1 , Acetil-CoA Carboxilase/metabolismo , Adipogenia/efeitos dos fármacos , Tecido Adiposo/citologia , Animais , Regulação da Expressão Gênica , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipogênese/efeitos dos fármacos , Camundongos , Triglicerídeos/metabolismoRESUMO
The global rise in obesity rates is alarming since this condition is associated with chronic low-grade inflammation and secondary comorbidities as glucose intolerance, cardiovascular disease and liver damage. Therefore, a lot of dietary approaches are proposed to prevent and to treat obesity and its associated disorders. Virgin coconut oil (VCO) is well known as a functional food due to its significant amounts of medium-chain triglycerides. This study aimed to evaluate the effect of VCO on adiposity, metabolic and inflammatory dysfunctions induced by a high-refined carbohydrate-containing (HC) diet in mice. Male BALB/c mice were divided into two groups and fed with control (C) or HC diet to induce obesity for eight weeks. At the 9th week mice fed with HC diet were randomly regrouped into four groups, and were kept this way until the 12th week, as following: (i) HC diet alone or HC diet supplemented with three different VCO doses (ii) 1000 mg/kg, (iii) 3000 mg/kg and (iv) 9000 mg/kg. Regardless of the concentration used, VCO supplementation promoted lower adiposity and also improvement in glucose tolerance, lower serum glucose and lipid levels and decreased hepatic steatosis. Moreover, VCO intake induced a lower inflammatory response due to decreased number of leukocytes and TNF-α and IL-6 concentrations in adipose tissue, as well as reduced counts of total leukocytes, mononuclear and polymorphonuclear circulating cells. Our data showed that VCO can be considered as an interesting potential dietary approach to attenuate obesity and its metabolic and inflammatory alterations.