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1.
PLoS Biol ; 22(1): e3002450, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38289899

RESUMO

Biological processes are intrinsically noisy, and yet, the result of development-like the species-specific size and shape of organs-is usually remarkably precise. This precision suggests the existence of mechanisms of feedback control that ensure that deviations from a target size are minimized. Still, we have very limited understanding of how these mechanisms operate. Here, we investigate the problem of organ size precision using the Drosophila eye. The size of the adult eye depends on the rates at which eye progenitor cells grow and differentiate. We first find that the progenitor net growth rate results from the balance between their proliferation and apoptosis, with this latter contributing to determining both final eye size and its variability. In turn, apoptosis of progenitor cells is hampered by Dpp, a BMP2/4 signaling molecule transiently produced by early differentiating retinal cells. Our genetic and computational experiments show how the status of retinal differentiation is communicated to progenitors through the differentiation-dependent production of Dpp, which, by adjusting the rate of apoptosis, exerts a feedback control over the net growth of progenitors to reduce final eye size variability.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/genética , Drosophila melanogaster , Proteínas de Drosophila/genética , Tamanho do Órgão , Retroalimentação , Olho , Retina , Apoptose/genética
2.
Biochimie ; 206: 105-115, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36273763

RESUMO

Snake envenomation is an ongoing global health problem and tropical neglected disease that afflicts millions of people each year. The only specific treatment, antivenom, has several limitations that affects its proper distribution to the victims and its efficacy against local effects, such as myonecrosis. The main responsible for this consequence are the phospholipases A2 (PLA2) and PLA2-like proteins, such as BthTX-I from Bothrops jararacussu. Folk medicine resorts to plants such as Tabernaemontana catharinensis to palliate these and other snakebite effects. Here, we evaluated the effect of its root bark extract and one of its isolated compounds, 12-methoxy-4-methyl-voachalotine (MMV), against the in vitro paralysis and muscle damage induced by BthTX-I. Secondary and quaternary structures of BthTX-I were not modified by the interaction with MMV. Instead, this compound interacted in an unprecedented way with the region inside the toxin hydrophobic channel and promoted a structural change in Val31, loop 58-71 and Membrane Disruption Site. Thus, we hypothesize that MMV inhibits PLA2-like proteins by preventing entrance of fatty acid into the hydrophobic channel. These data may explain the traditional use of T. catharinensis extract and confirm MMV as a promising candidate to complement antivenom or a structural guide to develop more effective inhibitors.


Assuntos
Bothrops , Venenos de Crotalídeos , Tabernaemontana , Animais , Antivenenos/farmacologia , Antivenenos/química , Tabernaemontana/metabolismo , Fosfolipases A2/química , Venenos de Serpentes , Venenos de Crotalídeos/química , Bothrops/metabolismo
3.
Nat Prod Res ; 36(11): 2907-2912, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34034579

RESUMO

Spiranthera odoratissima A. St.-Hil. (Rutaceae) has been popularly used against abdominal pain and rheumatism. This study aimed at extracting hexane from S. odoratissima (HE-SO) leaves to identify and quantify its volatile compounds by GC-MS and GC-FID and to evaluate its antifungal, antileishmanial and antibacterial activities in vitro. HE-SO exhibited antileishmanial activity against promastigote forms of Leishmania (Leishmania) amazonensis (IC50 = 38.16 µg/mL) and was moderately active against Xylella fastidiosa (MIC = 100 µg/mL). HE-SO also showed remarkable antifungal potential against six strains of Candida species, i. e., C. albicans, C. glabrata, C. parapsilosis, C. krusei, C. tropicalis and C. orthopsilosis. The lowest MIC values were between 31.25 and 250 µg/mL. Spathulenol (20.2%), τ-cadinol (11.7%), α-cadinol (9.4%), caryophyllene oxide (9.2%) and isoaromadendrene epoxide (8.2%) were the major components identified in HE-SO. Therefore, results showed that HE-SO has promising antileishmanial and antifungal actions.


Assuntos
Antiprotozoários , Leishmania mexicana , Leishmania , Óleos Voláteis , Rutaceae , Antifúngicos/química , Antiprotozoários/farmacologia , Candida , Candida glabrata , Hexanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Folhas de Planta/química , Xylella
4.
Int J Biol Macromol ; 185: 494-512, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34197854

RESUMO

Snakebite envenoming is the cause of an ongoing health crisis in several regions of the world, particularly in tropical and neotropical countries. This scenario creates an urgent necessity for new practical solutions to address the limitations of current therapies. The current study investigated the isolation, phytochemical characterization, and myotoxicity inhibition mechanism of gallic acid (GA), a myotoxin inhibitor obtained from Anacardium humile. The identification and isolation of GA was achieved by employing analytical chromatographic separation, which exhibited a compound with retention time and nuclear magnetic resonance spectra compatible with GA's commercial standard and data from the literature. GA alone was able to inhibit the myotoxic activity induced by the crude venom of Bothrops jararacussu and its two main myotoxins, BthTX-I and BthTX-II. Circular dichroism (CD), fluorescence spectroscopy (FS), dynamic light scattering (DLS), and interaction studies by molecular docking suggested that GA forms a complex with BthTX-I and II. Surface plasmon resonance (SPR) kinetics assays showed that GA has a high affinity for BthTX-I with a KD of 9.146 × 10-7 M. Taken together, the two-state reaction mode of GA binding to BthTX-I, and CD, FS and DLS assays, suggest that GA is able to induce oligomerization and secondary structure changes for BthTX-I and -II. GA and other tannins have been shown to be effective inhibitors of snake venoms' toxic effects, and herein we demonstrated GA's ability to bind to and inhibit a snake venom PLA2, thus proposing a new mechanism of PLA2 inhibition, and presenting more evidence of GA's potential as an antivenom compound.


Assuntos
Anacardium/química , Ácido Gálico/farmacologia , Miotoxicidade/tratamento farmacológico , Inibidores de Fosfolipase A2/farmacologia , Fosfolipases A2/metabolismo , Venenos de Serpentes/enzimologia , Animais , Modelos Animais de Doenças , Ácido Gálico/química , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Miotoxicidade/enzimologia , Miotoxicidade/etiologia , Inibidores de Fosfolipase A2/química , Fosfolipases A2/química , Caules de Planta/química , Proteínas de Répteis/química , Proteínas de Répteis/metabolismo , Ressonância de Plasmônio de Superfície
5.
Dev Biol ; 473: 90-96, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33581137

RESUMO

During development glial cell are crucially important for the establishment of neuronal networks. Proliferation and migration of glial cells can be modulated by neurons, and in turn glial cells can differentiate to assume key roles such as axonal wrapping and targeting. To explore the roles of actin cytoskeletal rearrangements in glial cells, we studied the function of Rho1 in Drosophila developing visual system. We show that the Pebble (RhoGEF)/Rho1/Anillin pathway is required for glia proliferation and to prevent the formation of large polyploid perineurial glial cells, which can still migrate into the eye disc if generated. Surprisingly, this Rho1 pathway is not necessary to establish the total glial membrane area or for the differentiation of the polyploid perineurial cells. The resulting polyploid wrapping glial cells are able to initiate wrapping of axons in the basal eye disc, however the arrangement and density of glia nuclei and membrane processes in the optic stalk are altered and the ensheathing of the photoreceptor axonal fascicles is reduced.


Assuntos
Axônios/fisiologia , Proteínas de Drosophila/metabolismo , Neuroglia/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Axônios/metabolismo , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Proteínas Contráteis/metabolismo , Drosophila melanogaster/metabolismo , Olho/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Neurogênese , Neuroglia/fisiologia , Neurônios/metabolismo , Poliploidia
6.
Toxicon X ; 7: 100049, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32613196

RESUMO

A bioactive compound isolated from the stem extract of Aristolochia sprucei through High Performance Liquid Chromatography (HPLC) was identified via Nuclear Magnetic Resonance (NMR) as the aristolochic acid (AA). This compound showed an inhibitory effect over the myotoxic activity of Bothrops jararacussu and Bothrops asper venoms, being also effective against the indirect hemolytic activity of B. asper venom. Besides, AA also inhibited the myotoxic activity of BthTX-I and MTX-II with an efficiency greater than 60% against both myotoxins. Docking predictions revealed an interesting mechanism, through which the AA displays an interaction profile consistent with its inhibiting abilities, binding to both active and putative sites of svPLA2. Overall, the present findings indicate that AA may bind to critical regions of myotoxic Asp 49 and Lys49-PLA2s from snake venoms, highlighting the relevance of domains comprising the active and putative sites to inhibit these toxins.

7.
Z Naturforsch C J Biosci ; 75(11-12): 377-387, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-32628640

RESUMO

This study aimed to evaluate the antibacterial and antibiotic-enhancing effects of the essential oil obtained from Ocimum gratissimum L. (OEOg) alone or in association with light-emitting diodes (LED) lights. The essential oil was obtained by hydrodistillation and its chemical composition analysed by gas chromatography coupled to mass spectrometry. The antibacterial and antibiotic-enhancing activities against multiresistant strains of Staphylococcus aureus and Escherichia coli were evaluated by the gaseous contact method. The analysis of the photoinductive effect on the antibacterial activity of the OEOg and antibiotics was assessed through exposure to different LED lights (red, blue and yellow). The phytochemical analysis identified five compounds, including eugenol, as the major constituent. The OEOg caused a significant inhibition of the halo, indicating a direct antibacterial effect. Exposure to the LED lights significantly enhanced the activity of the OEOg against E. coli. On the other hand, the action of the essential oil against S. aureus was enhanced by exposure to both blue and yellow lights. The effects of LED light exposure on the activity of conventional antibiotics varied significantly according to the drug and the bacterial strain. However, most combinations of LED lights and the OEOg presented synergistic effects against resistant bacterial strains, indicating enhanced antibacterial activity. Thus, these in vitro findings suggest that both OEOg and LED lights have promising antibacterial effects. Nevertheless, further research is required to evaluate in vivo the potential of these therapies for the treatment of infectious skin diseases.


Assuntos
Anti-Infecciosos/farmacologia , Farmacorresistência Bacteriana/genética , Ocimum/química , Óleos Voláteis/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/química , Farmacorresistência Bacteriana/efeitos dos fármacos , Sinergismo Farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade
8.
J Sci Food Agric ; 99(14): 6199-6208, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31250455

RESUMO

BACKGROUND: The Cerrado occupies 23% of Brazil. A. othonianum is a native Cerrado species that presents differently colored pseudofruits. This report describes the morphometric properties, physicochemical characterization, and phenolic and flavonoid compound compositions of 30 accessions of A. othonianum. RESULTS: The morphometric properties show that an average fruit had 21.97 mm length, 18.61 mm width, and 11.13 mm thickness, with 2.52 g mass. The pseudofruits had 28.84 mm apex width with 12.83 g of mass. The hue parameters of the pseudofruits were 18.67 ± 2.00 and 83.32 ± 1.97° (P < 0.05), reflecting their red to yellow color. The titratable acidity of the accessions was 0.91 ± 0.09 to 3.02 ± 0.02% (P < 0.05), soluble solid content was 9.60 ± 0.17 to 13.47 ± 0.38 °Brix (P < 0.05), and pH ranged from 2.83 ± 0.06 to 3.83 ± 0.06 (P < 0.05). Fourteen flavonoid compounds were identified. The most common compounds in the accessions were vitexin (93% of the accessions), hesperidin (57% of the accessions), epicatechin (34% of the accessions), and kaempferol-3-O-glucoside (30% of the accessions). Cluster analysis generated four groups with the traits ΔE, °h, C, soluble solid content, titratable acidity, pH, total flavonoids, and their identified compounds. CONCLUSIONS: Although all accessions are A. othonianum, there the chemical composition and the physical characteristics of these fruits vary. This is the first report in the literature using wild accessions. Greater disclosure of the species characteristic is interesting because it can increase income for the local population. © 2019 Society of Chemical Industry.


Assuntos
Anacardium/química , Frutas/química , Extratos Vegetais/química , Brasil , Cor , Flavonoides/química , Concentração de Íons de Hidrogênio , Fenóis/química
9.
Mol Cell Biol ; 39(12)2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-30988155

RESUMO

The nucleolus is a subnuclear compartment with key roles in rRNA synthesis and ribosome biogenesis, complex processes that require hundreds of proteins and factors. Alterations in nucleolar morphology and protein content have been linked to the control of cell proliferation and stress responses and, recently, further implicated in cell senescence and ageing. In this study, we report the functional role of NOL12 in the nucleolar homeostasis of human primary fibroblasts. NOL12 repression induces specific changes in nucleolar morphology, with increased nucleolar area but reduced nucleolar number, along with nucleolar accumulation and increased levels of fibrillarin and nucleolin. Moreover, NOL12 repression leads to stabilization and activation of p53 in an RPL11-dependent manner, which arrests cells at G2 phase and ultimately leads to senescence. Importantly, we found NOL12 repression in association with nucleolar stress-like responses in human fibroblasts from elderly donors, disclosing it as a biomarker in human chronological aging.


Assuntos
Envelhecimento/metabolismo , Nucléolo Celular/metabolismo , Fibroblastos/citologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Envelhecimento/genética , Pontos de Checagem do Ciclo Celular , Nucléolo Celular/genética , Células Cultivadas , Senescência Celular , Regulação para Baixo , Fibroblastos/metabolismo , Homeostase , Humanos , Masculino , Proteínas Ribossômicas/metabolismo , Proteína Supressora de Tumor p53/metabolismo
10.
Development ; 146(8)2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-30918051

RESUMO

The differentiation of tissues and organs requires that cells exchange information in space and time. Spatial information is often conveyed by morphogens: molecules that disperse across receiving cells to generate signalling gradients. Cells translate such concentration gradients into space-dependent patterns of gene expression and cellular behaviour. But could morphogen gradients also convey developmental time? Here, by investigating the developmental role of Hh on a component of the Drosophila visual system, the ocellar retina, we have discovered that ocellar cells use the non-linear gradient of Hh as a temporal cue, collectively performing the biological equivalent of a mathematical logarithmic transformation. In this way, a morphogen diffusing from a non-moving source is decoded as a wave of differentiating photoreceptors that travels at constant speed throughout the retinal epithelium.


Assuntos
Padronização Corporal/fisiologia , Proteínas de Drosophila/metabolismo , Proteínas Hedgehog/metabolismo , Transdução de Sinais/fisiologia , Animais , Padronização Corporal/genética , Drosophila , Proteínas de Drosophila/genética , Proteínas Hedgehog/genética , Modelos Teóricos , Retina/metabolismo , Transdução de Sinais/genética
11.
Chem Biodivers ; 16(1): e1800365, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30371987

RESUMO

This study aimed to isolate and identify flavonoids with hypoglycemic activity in Costus spiralis leaves. The methanolic extract (ME) was rich in flavonoids, while the powdered leaves (PL) contained considerable amounts of macro- and microelements. Oral acute treatment of streptozotocin (STZ)-induced diabetic rats for 18 h with the C. spiralis PL, ME and isolated guaijaverin (GUA) lowered glycemia, improved oral glucose tolerance and inhibited liver lipid peroxidation. GUA and ME lowered plasma levels of low-density and non-high density lipoproteins; GUA also lowered total cholesterol levels. PL, ME and GUA did not significantly alter the plasma levels of triglycerides, high-density lipoproteins, very low-density lipoproteins, creatinine and aspartate transaminase, and the total protein levels in the kidney and liver tissues. Therefore, C. spiralis leaves are promising raw materials and rich sources of bioactive flavonoids for the development of novel antidiabetic drugs due to their hypoglycemic, antidyslipidemic and antioxidant actions.


Assuntos
Glicemia/análise , Costus/química , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Flavonoides/uso terapêutico , Hipoglicemiantes/uso terapêutico , Lipídeos/sangue , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Animais , Antioxidantes/uso terapêutico , Aspartato Aminotransferases/sangue , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Teste de Tolerância a Glucose , Hipolipemiantes/uso terapêutico , Testes de Função Renal , Testes de Função Hepática , Masculino , Metanol/química , Ratos Wistar , Estreptozocina
12.
Dev Biol ; 442(1): 188-198, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30031756

RESUMO

Complex networks of signaling pathways maintain the correct balance between positive and negative growth signals, ensuring that tissues achieve proper sizes and differentiation pattern during development. In Drosophila, Dpp, a member of the TGFß family, plays two main roles during larval eye development. In the early eye primordium, Dpp promotes growth and cell survival, but later on, it switches its function to induce a developmentally-regulated cell cycle arrest in the G1 phase and neuronal photoreceptor differentiation. To advance in the identification and characterization of regulators and targets of Dpp signaling required for retinal development, we carried out an in vivo eye-targeted double-RNAi screen to identify punt (Type II TGFß receptor) interactors. Using a set of 251 genes associated with eye development, we identified CtBP, Dad, Ago and Brk as punt genetic interactors. Here, we show that downregulation of Ago, or conditions causing increased tissue growth including overexpression of Myc or CyclinD-Cdk4 are sufficient to partially rescue punt-dependent growth and photoreceptor differentiation. Interestingly, we show a novel role for the transcriptional co-repressor CtBP in inhibiting Dpp-dependent Mad activation by phosphorylation, downstream or in parallel to Dad, the inhibitory Smad. Furthermore, CtBP downregulation activates JNK signaling pathway, implying a complex regulation of signaling pathways by CtBP during eye development.


Assuntos
Receptores de Activinas Tipo II/fisiologia , Oxirredutases do Álcool/fisiologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/fisiologia , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/fisiologia , Fatores de Transcrição/metabolismo , Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Oxirredutases do Álcool/metabolismo , Animais , Diferenciação Celular/genética , Quinase 4 Dependente de Ciclina , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Olho/embriologia , Olho/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Morfogênese , Organogênese , Proteínas Repressoras/metabolismo , Transdução de Sinais/genética , Fatores de Transcrição/fisiologia , Fator de Crescimento Transformador beta/metabolismo
13.
Sci Rep ; 7(1): 4845, 2017 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-28687780

RESUMO

The specification and growth of organs is controlled simultaneously by networks of transcription factors. While the connection between these transcription factors with fate determinants is increasingly clear, how they establish the link with the cell cycle is far less understood. Here we investigate this link in the developing Drosophila eye, where two transcription factors, the MEIS1 homologue hth and the Zn-finger tsh, synergize to stimulate the proliferation of naïve eye progenitors. Experiments combining transcriptomics, open-chromatin profiling, motif analysis and functional assays indicate that these progenitor transcription factors exert a global regulation of the proliferation program. Rather than directly regulating cell cycle genes, they control proliferation through an intermediary layer of nuclear receptors of the ecdysone/estrogen-signaling pathway. This regulatory subnetwork between hth, tsh and nuclear receptors might be conserved from Drosophila to mammals, as we find a significant co-overexpression of their human homologues in specific cancer types.


Assuntos
Pontos de Checagem do Ciclo Celular , Proteínas de Drosophila/metabolismo , Drosophila/embriologia , Proteínas de Homeodomínio/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteínas Repressoras/metabolismo , Animais , Proliferação de Células , Cromatina/metabolismo , Olho/embriologia , Perfilação da Expressão Gênica , Transdução de Sinais
14.
PLoS Genet ; 13(3): e1006647, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28267791

RESUMO

In the nervous system, glial cells provide crucial insulation and trophic support to neurons and are important for neuronal survival. In reaction to a wide variety of insults, glial cells respond with changes in cell morphology and metabolism to allow repair. Additionally, these cells can acquire migratory and proliferative potential. In particular, after axonal damage or pruning the clearance of axonal debris by glial cells is key for a healthy nervous system. Thus, bidirectional neuron-glial interactions are crucial in development, but little is known about the cellular sensors and signalling pathways involved. In here, we show that decreased cellular fitness in retinal progenitors caused by reduced Drosophila Myc expression triggers non cell-autonomous activation of retinal glia proliferation and overmigration. Glia migration occurs beyond its normal limit near the boundary between differentiated photoreceptors and precursor cells, extending into the progenitor domain. This overmigration is stimulated by JNK activation (and the function of its target Mmp1), while proliferative responses are mediated by Dpp/TGF-ß signalling activation.


Assuntos
Proteínas de Ligação a DNA/fisiologia , Proteínas de Drosophila/fisiologia , Neuroglia/metabolismo , Neurônios/metabolismo , Células Fotorreceptoras de Invertebrados/metabolismo , Células-Tronco/metabolismo , Fatores de Transcrição/fisiologia , Animais , Apoptose , Axônios/metabolismo , Diferenciação Celular/fisiologia , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Matriz Extracelular/metabolismo , Feminino , MAP Quinase Quinase 4/metabolismo , Masculino , Neurogênese , Retina/citologia , Transdução de Sinais , Fatores de Transcrição/genética , Fator de Crescimento Transformador beta/metabolismo
15.
Open Biol ; 7(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28123053

RESUMO

Signalling by TGFß superfamily factors plays an important role in tissue growth and cell proliferation. In Drosophila, the activity of the TGFß/Activin signalling branch has been linked to the regulation of cell growth and proliferation, but the cellular and molecular basis for these functions are not fully understood. In this study, we show that both the RII receptor Punt (Put) and the R-Smad Smad2 are strongly required for cell and tissue growth. Knocking down the expression of Put or Smad2 in salivary glands causes alterations in nucleolar structure and functions. Cells with decreased TGFß/Activin signalling accumulate intermediate pre-rRNA transcripts containing internal transcribed spacer 1 regions accompanied by the nucleolar retention of ribosomal proteins. Thus, our results show that TGFß/Activin signalling is required for ribosomal biogenesis, a key aspect of cellular growth control. Importantly, overexpression of Put enhanced cell growth induced by Drosophila Myc, a well-characterized inducer of nucleolar hypertrophy and ribosome biogenesis.


Assuntos
Receptores de Activinas Tipo II/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Ribossomos/metabolismo , Glândulas Salivares/embriologia , Proteína Smad2/metabolismo , Receptores de Activinas Tipo II/genética , Ativinas/metabolismo , Animais , Ciclo Celular , Nucléolo Celular/metabolismo , Proliferação de Células , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Silenciamento de Genes , Glândulas Salivares/metabolismo , Transdução de Sinais , Proteínas Smad Reguladas por Receptor , Proteína Smad2/genética , Fator de Crescimento Transformador beta/metabolismo
16.
Glia ; 63(7): 1155-65, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25731761

RESUMO

Cellular migration and differentiation are important developmental processes that require dynamic cellular adhesion. Integrins are heterodimeric transmembrane receptors that play key roles in adhesion plasticity. Here, we explore the developing visual system of Drosophila to study the roles of integrin heterodimers in glia development. Our data show that αPS2 is essential for retinal glia migration from the brain into the eye disc and that glial cells have a role in the maintenance of the fenestrated membrane (Laminin-rich ECM layer) in the disc. Interestingly, the absence of glial cells in the eye disc did not affect the targeting of retinal axons to the optic stalk. In contrast, αPS3 is not required for retinal glia migration, but together with Talin, it functions in glial cells to allow photoreceptor axons to target the optic stalk. Thus, we present evidence that αPS2 and αPS3 integrin have different and specific functions in the development of retinal glia.


Assuntos
Comunicação Celular/fisiologia , Proteínas de Drosophila/metabolismo , Cadeias alfa de Integrinas/metabolismo , Neuroglia/fisiologia , Células Fotorreceptoras de Vertebrados/fisiologia , Animais , Animais Geneticamente Modificados , Axônios/fisiologia , Drosophila , Proteínas de Drosophila/genética , Imuno-Histoquímica , Cadeias alfa de Integrinas/genética , Microscopia Eletrônica de Transmissão , Interferência de RNA , Talina/metabolismo
17.
Chem Biol Interact ; 224: 136-41, 2014 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-25451592

RESUMO

We have investigated the in vitro anticandidal and antioxidant activities of phenolic compounds from Pyrostegia venusta flower extracts. We used the HPLC technique to purify the flavonoid (quercetin-3-O-α-l-rhamnopyranosyl-(1→6)-ß-d-galactopyranoside) and two phenylpropanoid glycosides (verbascoside and isoverbascoside); we evaluated the antimicrobial activity of the extracts against Candida strains (Candidaalbicans; Candidakrusei ATCC 6258; and the clinical isolate strains of Candida sp. C. albicans, C. krusei, Candidatropicalis, Candidaparapsilosis, and Candidaguilhermondii). The P. venusta flower extracts displayed antimicrobial and antioxidant activities. The semi-purified fraction of the P. venusta flower extract and the phenylpropanoid glycoside verbascoside exhibited activity similar to that of amphotericin B, which denoted that they are potentially applicable as natural antioxidant and anticandidal agents in the pharmaceutical industries.


Assuntos
Antifúngicos/farmacologia , Antioxidantes/farmacologia , Bignoniaceae/química , Candida/efeitos dos fármacos , Glucosídeos/farmacologia , Fenóis/farmacologia , Antifúngicos/química , Antifúngicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Dissacaridases/química , Dissacaridases/isolamento & purificação , Dissacaridases/farmacologia , Sinergismo Farmacológico , Glucosídeos/química , Glucosídeos/isolamento & purificação , Ligação de Hidrogênio , Fenóis/química , Fenóis/isolamento & purificação , Quercetina/análogos & derivados , Quercetina/química , Quercetina/isolamento & purificação , Quercetina/farmacologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-23737820

RESUMO

The antihyperglycemic effects of several plant extracts and herbal formulations which are used as antidiabetic formulations have been described and confirmed to date. The main objective of this work was to evaluate the hypoglycemic activity of the aqueous extract of Anacardium humile. Although the treatment of diabetic animals with A. humile did not alter body weight significantly, a reduction of the other evaluated parameters was observed. Animals treated with A. humile did not show variation of insulin levels, possibly triggered by a mechanism of blood glucose reduction. Levels of ALT (alanine aminotransferase) decreased in treated animals, suggesting a protective effect on liver. Levels of cholesterol were also reduced, indicating the efficacy of the extract in reestablishing the balance of nutrients. Moreover, a kidney protection may have been achieved due to the partial reestablishment of blood glucose homeostasis, while no nephrotoxicity could be detected for A. humile. The obtained results demonstrate the effectiveness of A. humile extracts in the treatment of alloxan-induced diabetic rats. Therefore, A. humile aqueous extract, popularly known and used by diabetic patients, induced an improvement in the biochemical parameters evaluated during and following treatment of diabetic rats. Thus, a better characterization of the medicinal potential of this plant will be able to provide a better understanding of its mechanisms of action in these pathological processes.

19.
Dev Biol ; 377(1): 154-65, 2013 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-23416177

RESUMO

Drosophila Decapentaplegic (Dpp), a member of the BMP2/4 class of the TGF-ßs, is required for organ growth, patterning and differentiation. However, much remains to be understood about the mechanisms acting downstream of these multiple roles. Here we investigate this issue during the development of the Drosophila eye. We have previously identified viriato (vito) as a dMyc-target gene encoding a nucleolar protein that is required for proper tissue growth in the developing eye. By carrying out a targeted in vivo double-RNAi screen to identify genes and pathways functioning with Vito during eye development, we found a strong genetic interaction between vito and members of the Dpp signaling pathway including the TGF-ß receptors tkv (type I), put (type II), and the co-Smad medea (med). Analyzing the expression of the Dpp receptor Tkv and the activation pattern of the pathway's transducer, p-Mad, we found that vito is required for a correct signal transduction in Dpp-receiving cells. Overall, we validate the use of double RNAi to find specific genetic interactions and, in particular, we uncover a link between the Dpp pathway and Vito, a nucleolar component. vito would act genetically downstream of Dpp, playing an important role in maintaining a sufficient level of Dpp activity for the promotion of eye disc growth and regulation of photoreceptor differentiation in eye development.


Assuntos
Diferenciação Celular , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/crescimento & desenvolvimento , Olho/citologia , Olho/crescimento & desenvolvimento , Proteínas Nucleares/metabolismo , Transdução de Sinais , Animais , Apoptose/genética , Padronização Corporal/genética , Diferenciação Celular/genética , Drosophila melanogaster/citologia , Drosophila melanogaster/genética , Feminino , Técnicas de Silenciamento de Genes , Genes de Insetos , Masculino , Interferência de RNA , Transdução de Sinais/genética
20.
Pharm Biol ; 50(3): 366-75, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22133075

RESUMO

CONTEXT: Sapindus saponaria L. (Sapindaceae) bark, root, and fruits are used as sedatives and to treat gastric ulcer and also demonstrate diuretic and expectorant effects. OBJECTIVE: The anti-snake venom properties of callus of S. saponaria are investigated here for the first time. MATERIALS AND METHODS: In vitro cultivated callus of Sapindus saponaria were lyophilized, and the extracts were prepared with different solvents, before submitting to phytochemical studies and evaluation of the anti-ophidian activity. Crude extracts were fractionated by liquid-liquid partition and the fractions were monitored by thin layer chromatography (TLC). Subsequently, anti-ophidian activities were analyzed toward Bothrops jararacussu Lacerda (Viperidae), B. moojeni Hoge (Viperidae), B. alternates Duméril (Viperidea) and Crotalus durissus terrificus Lineu (Viperidae) venoms and isolated myotoxins and phospholipase A(2) (PLA(2)). RESULTS: Fractions A1, A2 and the extract in MeOH:H(2)O (9:1) significantly inhibited the toxic and pharmacological activities induced by snake venoms and toxins, when compared to other extracts and fractions. The lethal, clotting, phospholipase, edema-inducing, hemorrhagic and myotoxic activities were partially inhibited by the different extracts and fractions. TLC profiles of the crude extracts (B and C) and fractions (A1 and A2) showed ß-sitosterol and stigmasterol as their main compounds. Stigmasterol exhibited inhibitory effects on enzymatic and myotoxic activities of PLA(2). DISCUSSION AND CONCLUSION: Sapindus saponaria extracts and fractions presented anti-ophidian activity and could be used as an adjuvant to serum therapy or for its supplementation, and in addition, as a rich source of potential inhibitors of enzymes involved in several pathophysiological human and animal diseases.


Assuntos
Antivenenos/farmacologia , Extratos Vegetais/farmacologia , Sapindus/química , Venenos de Víboras/antagonistas & inibidores , Animais , Antivenenos/isolamento & purificação , Bothrops , Cromatografia em Camada Fina , Crotalus , Masculino , Camundongos , Fosfolipases A2/metabolismo , Sitosteroides/isolamento & purificação , Sitosteroides/farmacologia , Estigmasterol/isolamento & purificação , Estigmasterol/farmacologia , Venenos de Víboras/toxicidade
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