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Wolbachia pipientis is a maternally transmitted symbiotic bacterium that mainly colonizes arthropods, potentially affecting different aspects of the host's physiology, e.g., reproduction, immunity, and metabolism. It has been shown that Wolbachia modulates glycogen metabolism in mosquito Aedes fluviatilis (Ae. fluviatilis). Glycogen synthesis is controlled by the enzyme GSK3, which is also involved in immune responses in both vertebrate and invertebrate organisms. Here we investigated the mechanisms behind immune changes mediated by glycogen synthase kinase ß (GSK3ß) in the symbiosis between Ae. fluviatilis and W. pipientis using a GSK3ß inhibitor or RNAi-mediated gene silencing. GSK3ß inhibition or knockdown increased glycogen content and Wolbachia population, together with a reduction in Relish2 and gambicin transcripts. Furthermore, knockdown of Relish2 or Caspar revealed that the immunodeficiency pathway acts to control Wolbachia numbers in the host. In conclusion, we describe for the first time the involvement of GSK3ß in Ae. fluviatilis immune response, acting to control the Wolbachia endosymbiotic population.
Assuntos
Aedes , Simbiose , Wolbachia , Wolbachia/fisiologia , Wolbachia/metabolismo , Aedes/microbiologia , Aedes/imunologia , Aedes/metabolismo , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Glicogênio/metabolismoRESUMO
The enzyme glucose-6-phosphate dehydrogenase (G6PDH) plays crucial roles in glucose homeostasis and the pentose phosphate pathway (PPP), being also involved in redox metabolism. The PPP is an important metabolic pathway that produces ribose and nicotinamide adenine dinucleotide phosphate (NADPH), which are essential for several physiologic and biochemical processes, such as the synthesis of fatty acids and nucleic acids. As a rate-limiting step in PPP, G6PDH is a highly conserved enzyme and its deficiency can lead to severe consequences for the organism, in particular for cell growth. Insufficient G6PDH activity can lead to cell growth arrest, impaired embryonic development, as well as a reduction in insulin sensitivity, inflammation, diabetes, and hypertension. While research on G6PDH and PPP has historically focused on mammalian models, particularly human disorders, recent studies have shed light on the regulation of this enzyme in arthropods, where new functions were discovered. This review will discuss the role of arthropod G6PDH in regulating redox homeostasis and immunometabolism and explore potential avenues for further research on this enzyme in various metabolic adaptations.
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The fat body is responsible for a variety of functions related to energy metabolism in arthropods, by controlling the processes of de novo glucose production (gluconeogenesis) and glycogen metabolism. The rate-limiting factor of gluconeogenesis is the enzyme phosphoenolpyruvate carboxykinase (PEPCK), generally considered to be the first committed step in this pathway. Although the study of PEPCK and gluconeogenesis has been for decades restricted to mammalian models, especially focusing on muscle and liver tissue, current research has demonstrated particularities about the regulation of this enzyme in arthropods, and described new functions. This review will focus on arthropod PEPCK, discuss different aspects to PEPCK regulation and function, its general role in the regulation of gluconeogenesis and other pathways. The text also presents our views on potentially important new directions for research involving this enzyme in a variety of metabolic adaptations (e.g. diapause), discussing enzyme isoforms, roles during arthropod embryogenesis, as well as involvement in vector-pathogen interactions, contributing to a better understanding of insect vectors of diseases and their control.
Assuntos
Artrópodes , Animais , Artrópodes/metabolismo , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Glucose/metabolismo , Homeostase , Mamíferos/metabolismoRESUMO
Recent advancements in molecular biology, particularly regarding massively parallel sequencing technologies, have enabled scientists to gain more insight into the physiology of ticks. While there has been progress in identifying tick proteins and the pathways they are involved in, the specificities of tick-host interaction at the molecular level are not yet fully understood. Indeed, the development of effective commercial tick vaccines has been slower than expected. While omics studies have pointed to some potential vaccine immunogens, selecting suitable antigens for a multi-antigenic vaccine is very complex due to the participation of redundant molecules in biological pathways. The expansion of ticks and their pathogens into new territories and exposure to new hosts makes it necessary to evaluate vaccine efficacy in unusual and non-domestic host species. This situation makes ticks and tick-borne diseases an increasing threat to animal and human health globally, demanding an urgent availability of vaccines against multiple tick species and their pathogens. This review discusses the challenges and advancements in the search for universal tick vaccines, including promising new antigen candidates, and indicates future directions in this crucial research field.
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Acaricide resistance is a global problem that has impacts worldwide. Tick populations with broad resistance to all commercially available acaricides have been reported. Since resistance selection in ticks and their role in pathogen transmission to animals and humans result in important economic and public health burden, it is essential to develop new strategies for their control (i.e., novel chemical compounds, vaccines, biological control). The synganglion is the tick central nervous system and it is responsible for synthesizing and releasing signaling molecules with different physiological functions. Synganglion proteins are the targets of the majority of available acaricides. In this review we provide an overview of the mode-of-action and resistance mechanisms against neurotoxic acaricides in ticks, as well as putative target sites in synganglion, as a supporting tool to identify new target proteins and to develop new strategies for tick control.
Assuntos
Acaricidas , Doenças dos Bovinos , Ixodidae , Rhipicephalus , Infestações por Carrapato , Vacinas , Animais , Humanos , Bovinos , Acaricidas/farmacologia , Controle de Ácaros e Carrapatos , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária , Doenças dos Bovinos/prevenção & controleRESUMO
Wolbachia pipientis is a maternally transmitted bacterium that mostly colonizes arthropods, including the mosquito Aedes fluviatilis, potentially affecting different aspects of host physiology. This intracellular bacterium prefers gonadal tissue cells, interfering with the reproductive cycle of insects, arachnids, crustaceans, and nematodes. Wolbachia's ability to modulate the host's reproduction is related to its success in prevalence and frequency. Infecting oocytes is essential for vertical propagation, ensuring its presence in the germline. The mosquito Ae. fluviatilis is a natural host for this bacterium and therefore represents an excellent experimental model in the effort to understand host-symbiont interactions and the mutual metabolic regulation. The aim of this study was to comparatively describe metabolic changes in naturally Wolbachia-infected and uninfected ovaries of Ae. fluviatilis during the vitellogenic period of oogenesis, thus increasing the knowledge about Wolbachia parasitic/symbiotic mechanisms.
Assuntos
Aedes , Wolbachia , Aedes/microbiologia , Animais , Oogênese , Simbiose/fisiologia , Wolbachia/fisiologiaRESUMO
Carbohydrate metabolism not only functions in supplying cellular energy but also has an important role in maintaining physiological homeostasis and in preventing oxidative damage caused by reactive oxygen species. Previously, we showed that arthropod embryonic cell lines have high tolerance to H2O2 exposure. Here, we describe that Rhipicephalus microplus tick embryonic cell line (BME26) employs an adaptive glucose metabolism mechanism that confers tolerance to hydrogen peroxide at concentrations too high for other organisms. This adaptive mechanism sustained by glucose metabolism remodeling promotes cell survival and redox balance in BME26 cell line after millimolar H2O2 exposure. The present work shows that this tick cell line could tolerate high H2O2 concentrations by initiating a carbohydrate-related adaptive response. We demonstrate that gluconeogenesis was induced as a compensation strategy that involved, among other molecules, the metabolic enzymes NADP-ICDH, G6PDH, and PEPCK. We also found that this phenomenon was coupled to glycogen accumulation and glucose uptake, supporting the pentose phosphate pathway to sustain NADPH production and leading to cell survival and proliferation. Our findings suggest that the described response is not atypical, being also observed in cancer cells, which highlights the importance of this model to all proliferative cells. We propose that these results will be useful in generating basic biological information to support the development of new strategies for disease treatment and parasite control.
Assuntos
Glucose , Rhipicephalus , Animais , Linhagem Celular , Gluconeogênese , Glucose/metabolismo , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , NADP/metabolismo , Oxirredução , Rhipicephalus/metabolismoRESUMO
INTRODUCTION: Metabolomic approaches can assess the actual state of an organism's energy metabolism during a specific morphological event, providing a more accurate insight into the correlations between physiology and metabolic regulation. METHODS: The study of the metabolomic profile aim to identify the largest possible number of biomolecules in a certain organism or specific structures. For this purpose, mass spectrometry (MS) and chromatography have been used in the present study. OBJECTIVES: In this context, the aim of the present work is to evaluate the glucose metabolomic profile during embryogenesis in Rhipicephalus microplus tick, investigating the dynamics of nutrient utilization during tick embryo formation, as well as the control of glucose metabolism. RESULTS: We show that glycogen reserves are preferentially mobilized to sustain the energy-intensive process of embryogenesis. Subsequently, the increase in concentration of specific amino acids indicates that protein degradation would provide carbons to fuel gluconeogenesis, supplying the embryo with sufficient glucose and glycogen during development. CONCLUSION: Altogether, these results demonstrated the presence of a very refined catabolic and anabolic control during embryogenesis in R. microplus tick, suggesting the pronounced gluconeogenesis as a strategy to secure embryo development. Moreover, this research contributes to the understanding of the mechanisms that control glucose metabolism during tick embryogenesis and may aid the identification of putative targets for novel chemical or immunological control methods, which are essential to improve the prevention of tick infestations.
Assuntos
Rhipicephalus , Infestações por Carrapato , Animais , Desenvolvimento Embrionário , Glucose , GlicogênioRESUMO
The mosquito Aedes aegypti undertakes a shift in carbohydrate metabolism during embryogenesis, including an increase in the activity of phosphoenolpyruvate carboxykinase (PEPCK), a key gluconeogenic enzyme, at critical steps of embryo development. All eukaryotes studied to date present two PEPCK isoforms, namely PEPCK-M (mitochondrial) and PEPCK-C (cytosolic). In A. aegypti, however, these proteins are so far uncharacterized. In the present work we describe two A. aegypti PEPCK isoforms by sequence alignment, protein modeling, and transcription analysis in different tissues, as well as PEPCK enzymatic activity assays in mitochondrial and cytoplasmic compartments during oogenesis and embryogenesis. First, we characterized the protein sequences compared to other organisms, and identified conserved sites and key amino acids. We also performed structure modeling for AePEPCK(M) and AePEPCK(C), identifying highly conserved structural sites, as well as a signal peptide in AePEPCK(M) localized in a very hydrophobic region. Moreover, after blood meal and during mosquito oogenesis and embryogenesis, both PEPCKs isoforms showed different transcriptional profiles, suggesting that mRNA for the cytosolic form is transmitted maternally, whereas the mitochondrial form is synthesized by the zygote. Collectively, these results improve our understanding of mosquito physiology and may yield putative targets for developing new methods for A. aegypti control.
Assuntos
Citosol/metabolismo , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Gluconeogênese , Glucose/metabolismo , Oogênese , Fosfoenolpiruvato Carboxiquinase (ATP)/metabolismo , Aedes , Sequência de Aminoácidos , Animais , Fosfoenolpiruvato Carboxiquinase (ATP)/genética , Filogenia , Isoformas de Proteínas , Homologia de SequênciaRESUMO
The indiscriminate use of acaricides is a problem worldwide and has increased the selection of acaricide-resistant tick populations. The goal of this study was to evaluate the acaricide effects of two essential oils (from Schinus molle and Bulnesia sarmientoi) using the larval immersion test on three Rhipicephalus tick species. Rhipicephalus evertsi, Rhipicephalus appendiculatus and Rhipicephalus pulchelus ticks collected in Kenya, without history of acaricide exposure, were tested, as well as individuals from two populations of Rhipicephalus microplus (with or without history of acaricide exposure), for comparison. The sample most resistant to the treatments was a population of R. microplus with previous acaricide exposure, whereas the least tolerant sample was a strain of the same species that never had contact with acaricides (Porto Alegre strain). Interestingly, the field tick samples without previous acaricide exposure responded to essential oils with a mortality profile resembling that observed in the acaricide-resistant R. microplus field population, and not the susceptible Porto Alegre strain. The essential oil of B. sarmientoi and its two components tested (guaiol and bulnesol) caused the highest mortality rates in the tested species and are potential molecules for future studies on control methods against these species.
Assuntos
Acaricidas , Óleos Voláteis , Rhipicephalus , Infestações por Carrapato , Acaricidas/farmacologia , Animais , Quênia , Óleos Voláteis/farmacologiaRESUMO
To further obtain insights into the Rhipicephalus microplus transcriptome, we used RNA-seq to carry out a study of expression in (i) embryos; (ii) ovaries from partially and fully engorged females; (iii) salivary glands from partially engorged females; (iv) fat body from partially and fully engorged females; and (v) digestive cells from partially, and (vi) fully engorged females. We obtained > 500 million Illumina reads which were assembled de novo, producing > 190,000 contigs, identifying 18,857 coding sequences (CDS). Reads from each library were mapped back into the assembled transcriptome giving a view of gene expression in different tissues. Transcriptomic expression and pathway analysis showed that several genes related in blood digestion and host-parasite interaction were overexpressed in digestive cells compared with other tissues. Furthermore, essential genes for the cell development and embryogenesis were overexpressed in ovaries. Taken altogether, these data offer novel insights into the physiology of production and role of saliva, blood digestion, energy metabolism, and development with submission of 10,932 novel tissue/cell specific CDS to the NCBI database for this important tick species.
Assuntos
Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Rhipicephalus/fisiologia , Animais , Bovinos , Feminino , Regulação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Especificidade de Órgãos , Ovário/química , Gravidez , Rhipicephalus/genética , Saliva/química , Análise de Sequência de RNARESUMO
Protease inhibitors play crucial roles in parasite development and survival, modulating the immune responses of their vertebrate hosts. Members of the serpin family are irreversible inhibitors of serine proteases and regulate systems related to defence against parasites. Limited information is currently available on protease inhibitors from the liver fluke Fasciola hepatica. In this study, we characterised four serpins from F. hepatica (FhS-1-FhS-4). Biochemical characterisation revealed that recombinant FhS-2 (rFhS) inhibits the activity of human neutrophil cathepsin G, while rFhS-4 inhibits the activity of bovine pancreatic chymotrypsin and cathepsin G. Consistent with inhibitor function profiling data, rFhS-4 inhibited cathepsin G-activated platelet aggregation in a dose-responsive manner.Similar to other serpins, rFhS2 and rFhS-4 bind to heparin with high affinity. Tissue localisation demonstrated that these serpins have different spatial distributions. FhS-2 is localised in the ovary, while FhS-4 was found in gut cells. Both of them co-localised in the spines within the tegument. These findings provide the basis for study of functional roles of these proteins as part of an immune evasion mechanism in the adult fluke, and in protection of eggs to ensure parasite life cycle continuity. Further understanding of serpins from the liver fluke may lead to the discovery of novel anti-parasitic interventions.
Assuntos
Fasciola hepatica , Interações Hospedeiro-Parasita , Serpinas , Animais , Catepsina G/antagonistas & inibidores , Bovinos , Quimotripsina/antagonistas & inibidores , Fasciola hepatica/enzimologia , Feminino , HumanosRESUMO
Several research groups around the world have studied diverse aspects of energy metabolism in arthropod disease vectors, with the aim of discovering potential control targets. As in all oviparous organisms, arthropod embryonic development is characterized by the mobilization of maternally-derived metabolites for the formation of new tissues and organs. Glycogen synthase kinase-3 (GSK-3) is a serine-threonine kinase described as an important regulator of metabolism and development in a wide range of organisms. GSK-3 was first identified based on its action upon glycogen synthase, a central enzyme in glycogen biosynthesis. Currently, it is recognized as a key component of multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription, cell migration, and immune response. The present review will describe the current knowledge on GSK-3 activation and its role in morphogenesis and embryonic metabolism in arthropods. Altogether, the information discussed here can spark new approaches and strategies for further studies, enhancing our understanding of these important arthropod vectors and strengthening the resources in the search for novel control methods.
Assuntos
Proteínas de Artrópodes/genética , Artrópodes/genética , Desenvolvimento Embrionário/genética , Quinase 3 da Glicogênio Sintase/genética , Morfogênese/genética , Animais , Proteínas de Artrópodes/metabolismo , Artrópodes/embriologia , Artrópodes/metabolismo , Embrião não Mamífero/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismoRESUMO
Embryogenesis is a metabolically intensive process carried out under tightly controlled conditions. The insulin signaling pathway regulates glucose homeostasis and is essential for reproduction in metazoan model species. Three key targets are part of this signaling pathway: protein kinase B (PKB, or AKT), glycogen synthase kinase 3 (GSK-3), and target of rapamycin (TOR). While the role of AKT and GSK-3 has been investigated during tick embryonic development, the role of TOR remains unknown. In this study, TOR and two other downstream effectors, namely S6 kinase (S6K) and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), were investigated in in vitro studies using the tick embryonic cell line BME26. First, we show that exogenous insulin can stimulate TOR transcription. Second, TOR chemical inhibition led to a decrease in BME26 cell viability, loss of membrane integrity, and downregulation of S6K and 4E-BP1 transcription. Conversely, treating BME26 cells with chemical inhibitors of AKT or GSK-3 did not affect S6K and 4E-BP1 transcription, showing that TOR is specifically required to activate its downstream targets. To address the role of TOR in tick reproduction, in vivo studies were performed. Analysis of relative transcription during different stages of tick embryonic development showed different levels of transcription for TOR, and a maternal deposition of S6K and 4E-BP1 transcripts. Injection of TOR double-stranded RNA (dsRNA) into partially fed females led to a slight delay in oviposition, an atypical egg external morphology, decreased vitellin content in eggs, and decreased larval hatching. Taken together, our data show that the TOR signaling pathway is important for tick reproduction, that TOR acts as a regulatory target in Rhipicephalus microplus embryogenesis and represents a promising target for the development of compounds for tick control.
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Reactive oxygen species (ROS) are natural byproducts of metabolism that have toxic effects well documented in mammals. In hematophagous arthropods, however, these processes are not largely understood. Here, we describe that Rhipicephalus microplus ticks and embryonic cell line (BME26) employ an adaptive metabolic compensation mechanism that confers tolerance to hydrogen peroxide (H2O2) at concentrations too high for others organisms. Tick survival and reproduction are not affected by H2O2 exposure, while BME26 cells morphology was only mildly altered by the treatment. Furthermore, H2O2-tolerant BME26 cells maintained their proliferative capacity unchanged. We evaluated several genes involved in gluconeogenesis, glycolysis, and pentose phosphate pathway, major pathways for carbohydrate catabolism and anabolism, describing a metabolic mechanism that explains such tolerance. Genetic and catalytic control of the genes and enzymes associated with these pathways are modulated by glucose uptake and energy resource availability. Transient increase in ROS levels, oxygen consumption, and ROS-scavenger enzymes, as well as decreased mitochondrial superoxide levels, were indicative of cell adaptation to high H2O2 exposure, and suggested a tolerance strategy developed by BME26 cells to cope with oxidative stress. Moreover, NADPH levels increased upon H2O2 challenge, and this phenomenon was sustained mainly by G6PDH activity. Interestingly, G6PDH knockdown in BME26 cells did not impair H2O2 tolerance, but generated an increase in NADP-ICDH transcription. In agreement with the hypothesis of a compensatory NADPH production in these cells, NADP-ICDH knockdown increased G6PDH relative transcript level. The present study unveils the first metabolic evidence of an adaptive mechanism to cope with high H2O2 exposure and maintain redox balance in ticks.
Assuntos
Metabolismo dos Carboidratos/fisiologia , Peróxido de Hidrogênio/toxicidade , Oxidantes/toxicidade , Estresse Oxidativo/fisiologia , Rhipicephalus/metabolismo , Adaptação Fisiológica , Animais , Carboidratos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Resistência a Medicamentos , Tolerância a Medicamentos/fisiologia , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , NADP/análise , OxirreduçãoRESUMO
The mosquito Aedes aegypti is vector of several viruses including yellow fever virus, dengue virus chikungunya virus and Zika virus. One of the major problems involving these diseases transmission is that A. aegypti embryos are resistant to desiccation at the end of embryogenesis, surviving and remaining viable for several months inside the egg. Therefore, a fine metabolism control is essential to support these organisms throughout this period of resistance. The carbohydrate metabolism has been shown to be of great importance during arthropod embryogenesis, changing dramatically in order to promote growth and differentiation and in periods of resistance. This study investigated fundamental aspects of glucose metabolism in three stages of A. aegypti egg development: pre-desiccated, desiccated, and rehydrated. The activities of regulatory enzymes in carbohydrate metabolism such as pyruvate kinase, hexokinase and glucose 6-phosphate dehydrogenase were evaluated. We show that these activities were reduced in A. aegypti desiccated eggs, suggesting a decreased activity of glycolytic and pentose phosphate pathway. In contrast, gluconeogenesis increased in desiccated eggs, which uses protein as substrate to synthesize glucose. Accordingly, protein amount decreased during this stage, while glucose levels increased. Glycogen content, a major carbohydrate reserve in mosquitoes, was evaluated and shown to be lower in desiccated and rehydrated eggs, indicating it was used to supply energy metabolism. We observed a reactivation of carbohydrate catabolism and an increased gluconeogenesis after rehydration, suggesting that controlling glucose metabolism was essential not only to survive the period of desiccation, but also for subsequent larvae hatch. Taken together, these results contribute to a better understanding of metabolism regulation in A. aegypti eggs during desiccation periods. Such regulatory mechanisms enable higher survival rate and consequently promote virus transmission by these important disease vectors, making them interesting subjects in the search for novel control methods.
Assuntos
Aedes/crescimento & desenvolvimento , Aedes/fisiologia , Embrião não Mamífero/fisiologia , Metabolismo Energético , Gluconeogênese , Glicólise , Aedes/embriologia , Aedes/enzimologia , Animais , Dessecação , Embrião não Mamífero/enzimologia , Desenvolvimento Embrionário , Regulação da Expressão Gênica no Desenvolvimento , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Larva/enzimologia , Larva/crescimento & desenvolvimento , Larva/fisiologia , Estado de Hidratação do Organismo , Via de Pentose Fosfato , Filogenia , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , Estresse Fisiológico , Análise de SobrevidaRESUMO
The cattle tick R. microplus is the biggest obstacle to livestock rearing in tropical countries. It is responsible for billions of dollars in losses every year, affecting meat and milk production, beef and dairy cattle, and the leather industry. The lack of knowledge and strategies to combat the tick only increases the losses, it leads to successive and uncontrolled applications of acaricides, favouring the selection of strains resistant to commercially available chemical treatments. In this paper, we tested 3bromopyruvate (3BrPA), an alkylating agent with a high affinity for cysteine residues, on the R. microplus metabolism. We found that 3-BrPA was able to induce cell death in an assay using BME26 strain cell cultures derived from embryos, it was also able to reduce cellular respiration in developing embryos. 3-BrPA is a nonspecific inhibitor, affecting enzymes of different metabolic pathways in R. microplus. In our experiments, we demonstrated that 3-BrPA was able to affect the glycolytic enzyme hexokinase, reducing its activity by approximately 50%; and it strongly inhibited triose phosphate isomerase, which is an enzyme involved in both glycolysis and gluconeogenesis. Also, the mitochondrial respiratory chain was affected, NADH cytochrome c reductase (complex I-III) and succinate cytochrome c reductase (complex II-III) were strongly inhibited by 3-BrPA. Glutamate dehydrogenase was also affected by 3-BrPA, showing a gradual inhibition of activity in all the 3-BrPA concentrations tested. Altogether, these results show that 3-BrPA is a harmful compound to the tick organism.
Assuntos
Metabolismo Energético/efeitos dos fármacos , Piruvatos/farmacologia , Rhipicephalus/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Consumo de OxigênioRESUMO
The cattle tick Rhipicephalus (Boophilus) microplus is an ectoparasite capable of transmitting a large number of pathogens, causing considerable losses in the cattle industry, with substantial damage to livestock. Over the years, important stages of its life cycle, such as the embryo, have been largely ignored by researchers. Tick embryogenesis has been typically described as an energy-consuming process, sustaining cell proliferation, differentiation, and growth. During the embryonic stage of arthropods, there is mobilization of metabolites of maternal origin for the development of organs and tissues of the embryo. Glycogen resynthesis in late embryogenesis is considered as an effective indicator of embryonic integrity. In the cattle tick R.(B. (B.) microplus, glycogen resynthesis is sustained by protein degradation through the gluconeogenesis pathway at the end of the embryonic period. Despite recent advancements in research on tick energy metabolism at the molecular level, the dynamics of nutrient utilization during R. (B.) microplus embryogenesis is still poorly understood. The present review aims to describe the regulatory mechanisms of carbohydrate metabolism during maternal-zygotic transition and identify possible new targets for the development of novel drugs and other control measures against R. (B.) microplus infestations.(AU)
O carrapato bovino Rhipicephalus (B.) microplus é um ectoparasita capaz de transmitir diversos patógenos, sendo responsável por grandes perdas na pecuária pelos danos causados ao gado. Atualmente, muitos estudos têm negligenciado fases importantes do ciclo de vida deste parasita, como a fase embrionária. A embriogênese é classicamente descrita como um processo que demanda um consumo de energia, possibilitando a proliferação celular, diferenciação e crescimento. Além disso, em artrópodes, o estágio da embriogênese é caracterizado pela mobilização de metabolitos de origem materna para o desenvolvimento de novos tecidos e órgãos. A ressíntese de glicogênio no final da embriogênese tem sido descrita em diversas espécies de artrópodes, sendo considerada um indicador de integridade do embrião. No caso do R. (B.) microplus a ressíntese de glicogênio é sustentada pela degradação de proteínas durante a gliconeogênese, no terço final da embriogênese. Apesar dos recentes avanços, no estudo molecular e do metabolismo energético, os mecanismos envolvidos na dinâmica da utilização de diferentes substratos energéticos durante a embriogênese do carrapato R. (B.) microplus ainda é pouco entendido. Diante deste panorama, estudos que descrevam a regulação destes mecanismos e da associação do metabolismo de carboidratos com a transição materno zigótica, pode auxiliar na busca de novos alvos para o desenvolvimento de novos acaricidas e outras intervenções para o controle infestações de R. (B.) microplus.(AU)
Assuntos
Rhipicephalus , Metabolismo Energético , Desenvolvimento EmbrionárioRESUMO
Abstract The cattle tick Rhipicephalus (Boophilus) microplus is an ectoparasite capable of transmitting a large number of pathogens, causing considerable losses in the cattle industry, with substantial damage to livestock. Over the years, important stages of its life cycle, such as the embryo, have been largely ignored by researchers. Tick embryogenesis has been typically described as an energy-consuming process, sustaining cell proliferation, differentiation, and growth. During the embryonic stage of arthropods, there is mobilization of metabolites of maternal origin for the development of organs and tissues of the embryo. Glycogen resynthesis in late embryogenesis is considered as an effective indicator of embryonic integrity. In the cattle tick R.(B. (B.) microplus, glycogen resynthesis is sustained by protein degradation through the gluconeogenesis pathway at the end of the embryonic period. Despite recent advancements in research on tick energy metabolism at the molecular level, the dynamics of nutrient utilization during R. (B.) microplus embryogenesis is still poorly understood. The present review aims to describe the regulatory mechanisms of carbohydrate metabolism during maternal-zygotic transition and identify possible new targets for the development of novel drugs and other control measures against R. (B.) microplus infestations.
Resumo O carrapato bovino Rhipicephalus (B.) microplus é um ectoparasita capaz de transmitir diversos patógenos, sendo responsável por grandes perdas na pecuária pelos danos causados ao gado. Atualmente, muitos estudos têm negligenciado fases importantes do ciclo de vida deste parasita, como a fase embrionária. A embriogênese é classicamente descrita como um processo que demanda um consumo de energia, possibilitando a proliferação celular, diferenciação e crescimento. Além disso, em artrópodes, o estágio da embriogênese é caracterizado pela mobilização de metabolitos de origem materna para o desenvolvimento de novos tecidos e órgãos. A ressíntese de glicogênio no final da embriogênese tem sido descrita em diversas espécies de artrópodes, sendo considerada um indicador de integridade do embrião. No caso do R. (B.) microplus a ressíntese de glicogênio é sustentada pela degradação de proteínas durante a gliconeogênese, no terço final da embriogênese. Apesar dos recentes avanços, no estudo molecular e do metabolismo energético, os mecanismos envolvidos na dinâmica da utilização de diferentes substratos energéticos durante a embriogênese do carrapato R. (B.) microplus ainda é pouco entendido. Diante deste panorama, estudos que descrevam a regulação destes mecanismos e da associação do metabolismo de carboidratos com a transição materno zigótica, pode auxiliar na busca de novos alvos para o desenvolvimento de novos acaricidas e outras intervenções para o controle infestações de R. (B.) microplus.