Inhibition Of acetyl-CoA Carboxylase Research Articles

THE IMPACT OF ESSENTIAL OILS OF THE LAMIACEAE FAMILY AGAINST TYLENCHULUS SEMIPENETRANS USING MOLECULAR MODELING METHODS

Tylenchulus semipenetrans is an economically important plant-parasitic nematode occurring in all citrus-producing regions of the world and causing a disease called “slow decline”. Chemical nematicides commonly used in agriculture have ecotoxicological effects. As a control method, attention has been paid to bio-nematicides that do not exhibit harmful effects on the ecosystem. In this study we will carry out the in scilico experiments in order to find the most coherent Enzyme-Ligand complex to lead to the best inhibitors of Acetyl CoA Carboxylase in Citrus Tylenchulus semipenetrans nematode. “Acetyl CoA Carboxylase” enzyme responsible for fatty acid synthesis in Tylenchulus semipenetrans, its alteration disrupting the synthesis of the surface layer, this inhibitory action is based on essential oils of aromatic plants, taking as an example the Lamiaceae family, using natural compounds extract from essential oils of Salvia verbenaca, Lavandula stoechas, Rosmarinus officinalis, and Thymus ciliatus. This study revealed for the first time that ?-phellandrène from Salvia verbenaca gives the best docking scores compared to Biotine, the co-crystallized inhibitor of the Acetyl CoA Carboxylase, to spirotetramat as chemical insecticide already used against citrus nematode, and to the other complexes. After that, the Molecular Dynamics Simulation study showed a good result for the ?-phellandrène- Acetyl CoA Carboxylase docked complex, for that we can consider that ?-phellandrène extracted from Salvia verbenaca’s essential oil as a functional inhibitor of Acetyl CoA Carboxylase activities and it can be used as good bio-nematicides against Tylenchulus semipenetrans.

Effects of in vivo phlorizin treatment and in vitro addition of carnitine, propionate, acetate, and 5-tetradecyloxy-2-furoic acid on palmitate metabolism in ovine hepatocytes

Modulatory effects of l-carnitine, acetate, propionate, and 5-tetradecyloxy-2-furoic acid (TOFA; an inhibitor of acetyl-CoA carboxylase) on oxidation and esterification of [1-14C]-palmitate were studied in hepatocytes isolated from phlorizin-treated and control wethers. Our hypotheses were that (1) palmitate oxidation would be greater in hepatocytes from sheep injected with phlorizin; (2) l-carnitine would increase palmitate oxidation more in hepatocytes from sheep injected with phlorizin; and (3) acetate and propionate would decrease oxidation in sheep hepatocytes partly through action of acetyl-CoA carboxylase. Palmitate metabolism did not differ between cells from control and those from phlorizin-treated wethers. Carnitine increased oxidation of palmitate to CO2 and acid-soluble products (ASP; mainly ketone bodies) and decreased esterification of palmitate in isolated hepatocytes from both groups of wethers, but the increase in oxidation to ASP was greater in cells from phlorizin-treated wethers. Propionate increased palmitate oxidation to CO2 in phlorizin-treated wethers. Propionate increased oxidation of palmitate to ASP in control wethers but decreased oxidation to ASP in phlorizin-treated wethers. Propionate increased esterification of palmitate to total esterified products and triglyceride, and the effect was larger in phlorizin-treated wethers. Acetate decreased palmitate esterification to total esterified products in control wethers, but the effect was blunted in phlorizin-treated wethers. Acetate did not affect palmitate oxidation. Addition of TOFA increased production of triglyceride from palmitate in the presence of propionate. The lack of interaction between TOFA and propionate indicates that propionate does not inhibit carnitine palmitoyltransferase I via cytosolic generation of methylmalonyl-CoA by acetyl-CoA carboxylase. In conclusion, although in vivo phlorizin treatment did not affect in vitro metabolism of palmitate by isolated ovine hepatocytes, phlorizin increased the stimulatory effect of carnitine on oxidation of palmitate to ASP and the inhibitory effect of propionate on oxidation of palmitate to ASP. Metabolism of acetate and propionate by acetyl-CoA carboxylase did not affect palmitate oxidation or esterification. Results provide additional insight into control of fatty acid metabolism in hepatocytes.

Quantification of Multiple Herbicide Resistance in Phalaris minor Populations of the North-Western Indo-Gangetic Plains of India

Multiple resistance to different herbicides used for management of Phalaris minor Retz. in Northern India was quantified for its two populations—one susceptible and the other resistant to acetyl-CoA carboxylase (ACCase) inhibitor herbicide clodinafop-propargyl. Clodinafop-propargyl and pinoxaden at their recommended dose recorded complete control of clodinafop-propargyl susceptible P. minor population, whereas sulfosulfuron and mesosulfuron plus iodosulfuron at their recommended dose exhibited 48.5 and 51.5% control of this population. In clodinafop-propargyl-resistant P. minor population, sulfosulfuron and mesosulfuron plus iodosulfuron even at 4X dose did not cause any mortality; however, pinoxaden at 4X dose caused complete mortality at 30 DAS. Metribuzin plus clodinafop-propargyl applied at all the doses (0.25X, 0.5X, X, 2X and 4X) recorded complete mortality of both the populations. Application of different herbicides caused reduction in chlorophyll fluorescence and chlorophyll content index in leaves of both the populations in a dose-dependent manner. But the magnitude of reduction was higher in susceptible population as compared to the resistant population.

The Role of Sugar Signaling in Regulating Plant Fatty Acid Synthesis.

Photosynthates such as glucose, sucrose, and some of their derivatives play dual roles as metabolic intermediates and signaling molecules that influence plant cell metabolism. Such sugars provide substrates for de novo fatty acid (FA) biosynthesis. However, compared with the well-defined examples of sugar signaling in starch and anthocyanin synthesis, until recently relatively little was known about the role of signaling in regulating FA and lipid biosynthesis. Recent research progress shows that trehalose 6-phosphate and 2-oxoglutarate (2-OG) play direct signaling roles in the regulation of FA biosynthesis by modulating transcription factor stability and enzymatic activities involved in FA biosynthesis. Specifically, mechanistic links between sucrose non-fermenting−1–related protein kinase 1 (SnRK1)–mediated trehalose 6-phosphate (T6P) sensing and its regulation by phosphorylation of WRI1 stability, diacylglycerol acyltransferase 1 (DGAT1) enzyme activity, and of 2-OG–mediated relief of inhibition of acetyl-CoA carboxylase (ACCase) activity by protein PII are exemplified in detail in this review.

Confirmation of Multiple Resistant Chloris radiata Population, Harvested in Colombian Rice Fields

This paper reports the first C. radiata population with resistance to glyphosate and multiple resistance to the acetolactate synthase (ALS) inhibitor, imazamox. Two populations, one putative resistant (R) and one susceptible (S), were used in the studies. Dose–response experiments were performed to evaluate the resistance factor (RF). Shikimic acid accumulation, 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) and ALS enzyme activities were studied together with chemical integrated weed management (adjuvants and alternative herbicides). The resistance to glyphosate and imazamox was confirmed based on the dry weight reduction, visual evaluation and survival. The results of dose–response curve assays showed for the R population intermedium RF for glyphosate (5.1 and 9.7 for amount of herbicide needed to reduce the dry weight by 50% GR50 and lethal dose of 50% LD50, respectively) and high RF for imazamox (34.9 and 37.4, respectively). The low shikimic acid accumulation in R population confirmed the glyphosate resistance. The glyphosate concentration which inhibited the EPSPS enzyme in 50% (I50) was approximately 20 times higher for R population than the S population, while the imazamox I50 in ALS enzyme for the R plants was 89 times greater than the S plants. In the chemical integrated weed management, the foliar retention and effectivity assays showed that the use of adjuvants improves the retention of glyphosate and imazamox, and the reduction in dry weight of weeds. The alternative herbicides study showed that the acetyl-CoA carboxylase (ACCase) inhibitors, paraquat and glufosinate, had better results for control in this species. However, poor control was observed with bispyribac-sodium, metsulfuron-methyl and quinclorac, indicating possible cross-resistance for ALS-inhibitors and also multiple resistance for auxinic herbicides (quinclorac). Nevertheless dose–response experiments are required to confirm this assumption.

Biotin attachment domain-containing proteins mediate hydroxy fatty acid-dependent inhibition of acetyl CoA carboxylase

Hundreds of naturally occurring specialized fatty acids (FAs) have potential as desirable chemical feedstocks if they could be produced at large scale by crop plants; however, transgenic expression of their biosynthetic genes has generally been accompanied by dramatic reductions in oil yield. For example, expression of castor (Ricinus communis) FA hydroxylase (FAH) in the Arabidopsis thaliana FA elongation mutant fae1 resulted in a 50% reduction of FA synthesis rate that was attributed to inhibition of acetyl-CoA carboxylase (ACCase) by an undefined mechanism. Here, we tested the hypothesis that the ricinoleic acid-dependent decrease in ACCase activity is mediated by biotin attachment domain-containing (BADC) proteins. BADCs are inactive homologs of biotin carboxy carrier protein that lack a biotin cofactor and can inhibit ACCase. Arabidopsis contains three BADC genes. To reduce expression levels of BADC1 and BADC3 in fae1/FAH plants, a homozygous badc1,3/fae1/FAH line was created. The rate of FA synthesis in badc1,3/fae1/FAH seeds doubled relative to fae1/FAH, restoring it to fae1 levels, increasing both native FA and HFA accumulation. Total FA per seed, seed oil content, and seed yield per plant all increased in badc1,3/fae1/FAH, to 5.8 µg, 37%, and 162 mg, respectively, relative to 4.9 µg, 33%, and 126 mg, respectively, for fae1/FAH. Transcript levels of FA synthesis-related genes, including those encoding ACCase subunits, did not significantly differ between badc1,3/fae1/FAH and fae1/FAH. These results demonstrate that BADC1 and BADC3 mediate ricinoleic acid-dependent inhibition of FA synthesis. We propose that BADC-mediated FAS inhibition as a general mechanism that limits FA accumulation in specialized FA-accumulating seeds.

Multiple Herbicide Resistance Evolution: The Case of Eleusine indica in Brazil.

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 ∼38% 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.

Synthesis and biological evaluation of 4-phenoxy-phenyl isoxazoles as novel acetyl-CoA carboxylase inhibitors

Acetyl-CoA carboxylase (ACC) is a crucial enzyme in fatty acid metabolism, which plays a major role in the occurrence and development of certain tumours. Herein, one potential ACC inhibitor (6a) was identified through high-throughput virtual screening (HTVS), and a series of 4-phenoxy-phenyl isoxazoles were synthesised for structure-activity relationship (SAR) studies. Among these compounds, 6g exhibited the most potent ACC inhibitory activity (IC50=99.8 nM), which was comparable to that of CP-640186. Moreover, the antiproliferation assay revealed that compound 6l exhibited the strongest cytotoxicity, with IC50 values of 0.22 µM (A549), 0.26 µM (HepG2), and 0.21 µM (MDA-MB-231), respectively. The preliminary mechanistic studies on 6g and 6l suggested that the compounds decreased the malonyl-CoA levels, arrested the cell cycle at the G0/G1 phase, and induced apoptosis in MDA-MB-231 cells. Overall, these results indicated that the 4-phenoxy-phenyl isoxazoles are potential for further study in cancer therapeutics as ACC inhibitors.

The occurrence of herbicide-resistant Avena fatua (wild oats) populations to ACCase-inhibiting herbicides in Ireland

Following growers’ reports of herbicide control problems, populations of 30 wild oats, Avena fatua, were collected from the south-east main arable counties of Ireland in 2016 and investigated for the occurrence and potential for herbicide resistance to acetyl-CoA carboxylase (ACCase) inhibitors pinoxaden, propaquizafop and cycloxydim, as well as acetolactate synthase (ALS) inhibitor mesosulfuron + iodosulfuron. Plant survival ≥20% was considered as the discriminating threshold between resistant and susceptible populations, when plants were treated with full recommended field rates of ACCase/ALS inhibitors. Glasshouse sensitivity screens revealed 2 out of 30 populations were cross-resistant to all three ACCase inhibitors. While three populations were cross-resistant to both pinoxaden and propaquizafop, and additionally, two populations were resistant to propaquizafop only. Different degree of resistance and cross-resistance between resistant populations suggest the involvement of either different point mutations or more than one resistance mechanism. Nevertheless, all populations including the seven ACCase-resistant populations were equally susceptible to ALS inhibitor. An integrated weed management (cultural/non-chemical control tactics and judicious use of herbicides) approach is strongly recommended to minimize the risk of herbicide resistance evolution.

Blood meal drives de novo lipogenesis in the fat body of Rhodnius prolixus

In insects, lipids are stored in the fat body mainly as triacylglycerol. Lipids can be directly provided by digestion and incorporated from the hemolymph, or synthesized de novo from other substrates such as carbohydrates and amino acids. The first step in de novo lipid synthesis is catalyzed by acetyl-CoA carboxylase (ACC), which carboxylates acetyl-CoA to form malonyl-CoA. Rhodnius prolixus is a hematophagous insect vector of Chagas disease and feeds exclusively on large and infrequent blood meals. Adult females slowly digest the blood and concomitantly accumulate lipids in the fat body. In this study, we investigated the regulation of R. prolixus ACC (RhoprACC) expression and de novo lipogenesis activity in adult females at different nutritional and metabolic conditions. A phylogenetic analysis showed that insects, similar to other arthropods and unlike vertebrate animals, have only one ACC gene. In females on the fourth day after a blood meal, RhoprACC transcript levels were similar in the anterior and posterior midgut, fat body and ovary and higher in the flight muscles. In the fat body, gene expression was higher in fasted females and decreased after a blood meal. In the posterior midgut it increased after feeding, and no variation was observed in the flight muscle. RhoprACC protein content analysis of the fat body revealed a profile similar to the gene expression, with higher protein contents before feeding and in the first two days after a blood meal. Radiolabeled acetate was used to follow de novo lipid synthesis in the fat body and it was incorporated mainly into triacylglycerol, diacylglycerol and phospholipids. This lipogenic activity was inhibited by soraphen A, an ACC inhibitor, and it varied according to the insect metabolic status. De novo lipogenesis was very low in starved females and increased during the initial days after a blood meal. The flight muscles had a very low capacity to synthesize lipids when compared to the fat body. Radiolabeled leucine was also used as a substrate for de novo lipogenesis and the same lipid classes were formed. In conclusion, our results indicate that the blood meal induces the utilization of diet-derived amino acids by de novo lipogenesis in the fat body, and that the control of this activity does not occur at the RhoprACC gene or protein expression level.

Inhibition of Acetyl-CoA Carboxylase Causes Malformations in Rats and Rabbits: Comparison of Mammalian Findings and Alternative Assays.

Acetyl-CoA carboxylase (ACC) is an enzyme within the de novo lipogenesis (DNL) pathway and plays a role in regulating lipid metabolism. Pharmacologic ACC inhibition has been an area of interest for multiple potential indications including oncology, acne vulgaris, metabolic diseases such as type 2 diabetes mellitus, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. A critical role for ACC in de novo synthesis of long-chain fatty acids during fetal development has been demonstrated in studies in mice lacking Acc1, where the absence of Acc1 results in early embryonic lethality. Following positive predictions of developmental toxicity in the alternative in vitro assays (positive in murine embryonic stem cell [mESC] assay and rat whole embryo culture, but negative in zebrafish), developmental toxicity (growth retardation and dysmorphogenesis associated with disrupted midline fusion) was observed with the oral administration of the dual ACC1 and 2 inhibitors, PF-05175157, in Sprague Dawley rats and New Zealand White rabbits. The results of these studies are presented here to make comparisons across the assays, as well as mechanistic insights from the mESC assay demonstrating high ACC expression in the mESC and that ACC-induced developmental toxicity can be rescued with palmitic acid providing supportive evidence for DNL pathway inhibition as the underlying mechanism. Ultimately, while the battery of alternative approaches and weight-of-evidence case were useful for hazard identification, the embryo-fetal development studies were necessary to inform the risk assessment on the adverse fetal response, as malformations and/or embryo-fetal lethality were limited to doses that caused near-complete inhibition of DNL.

Synthesis and invitro evaluation of novel spiroketopyrazoles as acetyl-CoA carboxylase inhibitors and potential antitumor agents.

Acetyl-CoA carboxylase (ACC) is a rate-limiting enzyme in de novo fatty acid synthesis, which plays a critical role in the growth and survival of cancer cells. In this study, a series of spiroketopyrazole derivatives bearing quinoline moieties were synthesized, and invitro anticancer activities of these compounds as ACC inhibitors were evaluated. The biological evaluation showed that compound 7j exhibited the strongest enzyme inhibitory activity (IC50=1.29nM), while compound 7m displayed the most potent anti-proliferative activity against A549, HepG2, and MDA-MB-231cells with corresponding IC50 values of 0.55, 0.38, and 1.65μM, respectively. The preliminary pharmacological studies confirmed that compound 7m reduced the intracellular malonyl-CoA and TG levels in a dose-dependent manner. Moreover, it could down-regulate cyclin D1 and CDK4 to disturb the cell cycle and up-regulate Bax, caspase-3, and PARP along with the suppression of Bcl-2 to induce apoptosis. Notably, the combination of 7m with doxorubicin synergistically decreased the HepG2 cell viability. These results indicated that compound 7m as a single agent, or in combination with other antitumor drugs, might be a promising therapeutic agent for the treatment of hepatocellular carcinoma.

Nitrogen starvation–induced oxidative stress relieves PII-mediated inhibition of acetyl-CoA carboxylase (ACCase) activity and signals enhanced lipid synthesis in Synechococcus PCC 7942

The present study shows the existence of PII-acetyl-CoA carboxylase interaction in the cyanobacterium Synechococcus sp. PCC 7942 and the possible adverse impact of nitrogen starvation on this interaction. The in silico and in vitro analysis of PII-acetyl-CoA carboxylase interaction revealed that the biotin carboxyl carrier protein subunit of acetyl-CoA carboxylase enzyme actually interacts with the T-loop of PII protein. However, exposure of the cyanobacterium to nitrogen-starved condition showed a higher expression and activity of acetyl-CoA carboxylase at the intracellular level which denoted the impairment of PII-acetyl-CoA carboxylase interaction. A similar stimulatory effect of nitrogen starvation has also been noticed in the PII mutant of Synechococcus PCC 7942. Further, the physiological study reflected that nitrogen starvation–caused reactive oxygen species generation in the wild-type and PII mutant strains and lipid was increased in both strains of Synechococcus sp. PCC 7942. Proteomic analysis showed the upregulation of glycogen synthase, biotin carboxylase, and antioxidative enzymes and the deregulation of proteins involved in photosynthesis, energy metabolism, and protein synthesis. Interestingly, enhanced accumulation of transcripts of few tricarboxylic acid cycle genes was also noticed in the wild type. Although oxidative stress and lipid production were enhanced in both the test strains under nitrogen starvation, the impacts were more prominent in the mutant strain. Our results suggest that the nitrogen starvation–induced oxidative stress possibly relieved the PII-mediated inhibition of acetyl-CoA carboxylase and led to increased lipid synthesis in Synechococcus PCC 7942.

Tolerance to Some ACCase Inhibitors in Four Common Roegneria (Roegneria kamoji) Populations From China

Common roegneria, a perennial weed in Roegneria genera of the tribe Triticeae (family: Poaceae), is widely distributed in China and could not be effectively controlled by Acetyl coA carboxylase (ACCase) inhibitors in wheat in some regions. This study aimed to quantify herbicide tolerance level and investigate its mechanisms of ACCase tolerance in common roegneria. Whole-plant dose-response assay indicated that populations ZJJX and HBJZ (collected in wheat fields) exhibited high tolerance (ED50s>16-fold labeled field rate, LFR) to fenoxaprop-P-ethyl and clodinafop- propargyl (aryloxyphenoxypropionate, APPs), and pinoxaden (phenylpyrazolin, DEN). In addition, two populations collected from uncultivated areas, showed similar responses to these herbicides. All common roegneria populations were susceptible to haloxyfop-R-methyl and quizalofop-p-ethyl (APPs), clethodim and sethoxydim (cyclohexanedione, CHDs) (ED50s<1/2-fold LFR). The responses to ACCase inhibitors of common roegneria were in complete accord with wheat. ACCase sequencing revealed that the APPs tolerance was not conferred by known amino acid substitutions. The sensitivity of common roegneria populations to fenoxaprop-P-ethyl could not be reduced by metabolic inhibitors malathion and 4-chloro-7-nitro-benzoxadiazole. In vitro ACCase enzyme activity assays revealed that the activities of ACCase were increased in ZJJX, ZJHZ populations and wheat after fenoxaprop-P-ehtyl treatment, which at 72 h after treatment (HAT) was 1.46, 1.39 and 1.34-folds higher than that at 0 HAT, respectively. To our knowledge, this study reported for the first time the natural tolerance to ACCase inhibitors in common roegneria. The enhanced ACCase activity suggested that rapid metabolism of the herbicide might play an important role in the tolerance mechanism of this weed. Rotated with other crops (i.e. oilseed rape) to use different herbicides could serve as important tools for managing common roegneria in wheat.

Control of volunteer corn with rates of post-emergent ACCase inhibitors applied at different phenological stages

The occurrence of volunteer corn (Zea maysL.) has been common in Brazilian crops due to the adoption of a succession of soybean (Glycine max(L.) Merrill) and corn resistant to glyphosate. The aim of this work was to evaluate the control of volunteer corn using different rates of acetyl-CoAcarboxylase (ACCase) inhibitors herbicides at different phenological stages. The experiment was carried out in a greenhouse in a completely randomized design. The experiment was organized in a factorial scheme (3x7x2) with three herbicides (clethodim, quizalofop-P-tefuryl and clethodim + quizalofop-P-ethyl) applied atseven rates [0; 25; 50; 100; 200; 400 and 800 mL of commercial product (C.P.) ha-1], andat two corn phenological stages (V3 and V6). Visual control (%) assessments were carried out at 14, 21 and 28 days after application of treatments (DAT) and shoot dry mass (SDM) at 28 DAT. The data were submitted to analysis of variance and to complementary analysis by logistic regression adjustment. For allherbicides, the control of volunteer corn was greater at V3 stage, requiring lower rates compared to V6. Complete visual control of volunteer corn plants at V3 was obtained with rates of 25 mL C.P. ha-1for all herbicides evaluated, corresponding to 6, 3 and 6 + 3 g a.i. ha-1of clethodim, quizalofop-P-tefuryl and clethodim + quizalofop-P-ethyl, respectively. For V6 application, 400 mL C.P. ha-1of clethodim (equivalent to 96 g a.i. ha-1) and 100 mL C.P. ha-1of quizalofop-P-tefuryl (equivalent to 12 g a.i. ha-1) and clethodim + quizalofop-P-ethyl (equivalent to 24 + 12 g a.i. ha-1) were necessary to achieve 100% of plant mortality. Thus, the efficiency of clethodim was more dependent on the stage of application compared to others herbicides, requiring higher rates to achieve complete control of volunteer corn at V6.

Inhibition of Acetyl-CoA Carboxylase in Acutely Injured Tubular Cells Exacerbates DNA Damage and Mitochondria Fission in Diabetic Nephropathy

Inhibition of Acetyl-CoA Carboxylase in Acutely Injured Tubular Cells Exacerbates DNA Damage and Mitochondria Fission in Diabetic Nephropathy

OVIPOSITION OF Bactericera cockerelli (SULC) (HEMIPTERA: TRIOZIDAE) ON Capsicum chinense (JACQ) TREATED WITH SPIROMESIFEN OR SPIROTETRAMAT

El psílido de la papa/tomate, Bactericera cockerelli, es una de las plagas más importantes de cultivos de solanáceas en el mundo. Spirotetramat y spiromesifen son insecticidas comúnmente utilizados contra esta plaga y actúan inhibiendo la acetil CoA carboxilasa, y con ello evitan la biosíntesis de lípidos. Se evaluó el efecto de los insecticidas sobre el comportamiento de oviposición de B. cockerelli en plantas de chile habanero [Capsicum chinense (Jacq)]. El follaje de la planta se dividió en tres estratos (superior, medio e inferior) y todas las combinaciones de estratos se trataron por separado con 30 mL de la solución a una concentración de 1 mL L-1 de formulación comercial, se utilizó una torre Potter a 0.703 kg cm-2 de presión, calibrada para aplicar 2 mL cm-2. Después de 1 h de tratamiento se retiró la cubierta plástica de los estratos no tratados, y las plantas de cada tratamiento se infestaron con 20 pares de adultos de 20 a 24 h y se les permitió ovipositar durante 7 d. Se registró el número de huevos por hoja por estrato y se calculó su porcentaje. El porcentaje de huevos por hoja en el testigo en los estratos superior, medio e inferior fue 42, 32 y 26 %, respectivamente. El Spiromesifen inhibió significativamente (P ≤ 0.05) la oviposición sólo en la capa tratada. El Spirotetramat redujo significativamente (P ≤ 0.05) la tasa de oviposición, independientemente del estrato tratado, lo que indica actividad biológica en partes no tratadas de la planta, ya sea por encima o por debajo de la parte tratada.

Pharmacological ACC inhibition decreases thrombin-induced platelet aggregation by a mechanism independent of lipid content

Acetyl-CoA carboxylase (ACC) is the first committed enzyme regulating lipids synthesis. We have recently demonstrated that the overexpression of a constitutively active form of ACC in platelets leads to an increase in the phospholipid content which stimulates thrombus formation. Based on these data, we believe that ACC inhibition might be a counter-regulatory mechanism limiting endogenous lipogenesis and platelet reactivity in certain pathological circumstances. Our study aims to assess the impact of pharmacological ACC1 inhibition on platelet functions, de novo lipogenesis and lipid content. Platelets were treated with the long-chain fatty acid (FA) analog TOFA (30 μM) or the active site-directed CP640.186 (CP, 60 μM), two ACC inhibitors, for 2H before thrombin stimulation. Lipogenesis was measured via 14C-acetate incorporation into FA. Platelet functions were assessed by aggregometry. Lipidomics analysis was carried out on the commercial Lipidyzer platform. Both ACC inhibitors decreased lipogenesis and thrombin-induced platelet aggregation. TOFA, but not CP, drastically decreased mitochondrial oxygen consumption rate, an effect associated with an increased reactive oxygen species production and AMPK activation. Surprisingly, the quantitative lipidomics analyses showed that a preincubation with CP did not affect global platelet lipid content. However, the short-term ACC inhibition (and potential acetyl-CoA accumulation) was sufficient to modify the level of acetylated proteins such as tubulin, a key player in the regulation of platelet shape change and aggregation. Given the effect of TOFA on mitochondrial respiration, oxidative stress and AMPK activation, CP seems more appropriate to investigate the impact of ACC inhibition in platelets. A short-term acute treatment with CP inhibits thrombin-induced aggregation by a mechanism which doesn’t depend on lipid content but might involve changes in protein acetylation.

De novo lipogenesis is essential for platelet production in humans.

Acetyl-CoA carboxylase (ACC) catalyses the first step of de novo lipogenesis (DNL). Pharmacologic inhibition of ACC has been of interest for therapeutic intervention in a wide range of diseases. We demonstrate here that ACC and DNL are essential for platelet production in humans and monkeys, but in not rodents or dogs. During clinical evaluation of a systemically distributed ACC inhibitor, unexpected dose-dependent reductions in platelet count were observed. While platelet count reductions were not observed in rat and dog toxicology studies, subsequent studies in cynomolgus monkeys recapitulated these platelet count reductions with a similar concentration response to that in humans. These studies, along with ex vivo human megakaryocyte maturation studies, demonstrate that platelet lowering is a consequence of DNL inhibition likely to result in impaired megakaryocyte demarcation membrane formation. These observations demonstrate that while DNL is a minor quantitative contributor to global lipid balance in humans, DNL is essential to specific lipid pools of physiological importance.

Managing herbicide resistance in China

AbstractSince its initial introduction in the late 1950s, chemical control has dominated weed management practices in China. Not surprisingly, the development of herbicide resistance has become the biggest threat to long-term, sustainable weed management in China. Given that China has followed the same laissez-faire approach toward resistance management that has been practiced in developed countries such as the United States, herbicide resistance has evolved rapidly and increased steadily over the years. Previously, we carried out a systematic review to quantitatively assess herbicide-resistance issues in China. In this review, our main objective is to focus on mechanistic studies and management practices to document the (1) history of herbicide application in China; (2) resistance mechanisms governing the eight most resistance-prone herbicide groups, including acetolactate synthase inhibitors, acetyl-CoA carboxylase inhibitors, synthetic auxin herbicides, 5-enolpyruvylshikimate-3-phosphate synthase inhibitors, protoporphyrinogen oxidase inhibitors, photosystem I electron diverters, photosystem II inhibitors, and long-chain fatty-acid inhibitors; and (3) herbicide-resistance management strategies commonly used in China, including chemical, cultural, biological, physical, and integrated approaches. At the end, perspectives and future research are discussed to address the pressing need for the development of integrated herbicide-resistance management in China.