Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
J Exp Zool B Mol Dev Evol ; 342(4): 350-367, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38155515

RESUMO

In anurans, the vertebral column diverges widely from that of other tetrapods; yet the molecular mechanisms underlying its morphogenesis remain largely unexplored. In this study, we investigate the role of the homeologous uncx.L and uncx.S genes in the vertebral column morphogenesis of the allotetraploid frog Xenopus laevis. We initiated our study by cloning the uncx orthologous genes in the anuran Xenopus and determining their spatial expression patterns using in situ hybridization. Additionally, we employed gain-of-function and loss-of-function approaches through dexamethasone-inducible uncx constructs and antisense morpholino oligonucleotides, respectively. Comparative analysis of the messenger RNA sequences of homeologous uncx genes revealed that the uncx.L variant lacks the eh1-like repressor domain. Our spatial expression analysis indicated that in the presomitic mesoderm and somites, the transcripts of uncx.L and uncx.S are located in overlapping domains. Alterations in the function of uncx genes significantly impact the development and differentiation of the sclerotome and myotome, resulting in axial skeleton malformations. Our findings suggest a scenario where the homeologous genes uncx.L and uncx.S exhibit antagonistic functions during somitogenesis. Specifically, uncx.S appears to be crucial for sclerotome development and differentiation, while uncx.L primarily influences myotome development. Postallotetraploidization, the uncx.L gene in X. laevis evolved to lose its eh1-like repressor domain, transforming into a "native dominant negative" variant that potentially competes with uncx.S for the same target genes. Finally, the histological analysis revealed that uncx.S expression is necessary for the correct formation of pedicles and neural arch of the vertebrae, and uncx.L is required for trunk muscle development.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio , Proteínas de Xenopus , Xenopus laevis , Animais , Evolução Biológica , Somitos/metabolismo , Coluna Vertebral/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo
2.
Int J Dev Biol ; 65(1-2-3): 5-21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32930345

RESUMO

The history of science in Argentina is based on the enormous contribution that the great immigration of the 19th and 20th centuries produced in the country. The scientific and philosophical ideas and the role played especially by Italian scientists who arrived in the country produced a great impact on the different disciplines including Development Biology in emerging universities. The University of Tucumán pioneered the study of experimental biology, making important contributions to reproductive biology and to the early development of amphibians. The contribution of the Italian embryologist Armando Pisanó and the Argentinian Francisco D. Barbieri expanded the field to other universities and research centers located in Córdoba, La Plata, Bahía Blanca and Rosario. Given its strategic position, laboratories located in the city of Buenos Aires reached technological advances faster than others. Indeed, these laboratories saw the evolution from experimental biology to developmental genetics, renewing interest in this area. Currently, Developmental Biology brings together young researchers eager to consolidate regional and global collaboration networks that seek to help solve specific problems such as fertility, epigenetics, stem cells and tissue engineering.


Assuntos
Biologia do Desenvolvimento , Universidades , Argentina , Biologia do Desenvolvimento/tendências
3.
Int J Dev Biol ; 65(4-5-6): 177-186, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32930370

RESUMO

The axial skeleton of the anurans has undergone an evolutionary reduction of its bone elements. This structural plan is strongly preserved throughout the order and would have emerged as a highly specialized anatomical adaptation to its locomotor jumping pattern. The development programs that direct the vertebral morphogenesis of the anurans are poorly described and the molecular bases that have caused their pattern to differ from other tetrapods are completely unknown. In this work, we review the ontogeny of the spinal column of the anurans and explore the genetic mechanisms that could explain the morphological difference and the maintenance of the body plan during evolution. Here, we propose that the absence of caudal osseous elements, as a consequence of the inability of sclerotomes to form cartilaginous condensations in frogs, could be due to changes in both pattern and expression levels of Hox, Pax1, Pax9 and Uncx4.1 genes along the anteroposterior axis. The anteriorised expression of the Hox genes together with the reduction in the expression levels of Pax1, Pax9 and Uncx4 in the posterior somites could explain, at least partly, the loss of caudal vertebrae in the anurans during evolution.


Assuntos
Anuros , Regulação da Expressão Gênica no Desenvolvimento , Genes Homeobox , Esqueleto/anatomia & histologia , Animais , Anuros/anatomia & histologia , Anuros/genética , Osso e Ossos/anatomia & histologia , Somitos
4.
PLoS One ; 13(1): e0190509, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29300762

RESUMO

Drug repositioning or repurposing, i.e. identifying new indications for existing drugs, has gained increasing attention in the recent years. This approach enables the scientists to discover "new targets" for known drugs in a cost and time efficient manner. Glycation, the non-enzymatic reaction of sugars with proteins or nucleic acids to form early glycation (Amadori or fructosamine) products, is a key molecular basis of diabetic complications. Inhibiting the process of non-enzymatic protein glycation is one of the key strategies to prevent glycation-mediated diabetic complications. The present study focuses on the anti-glycation activity of 18 drugs, commonly used for the treatment of gastrointestinal, central nervous system, inflammatory diseases, bacterial infections, and gout. This study was carried out by using two in-vitro protein anti-glycation assay models. Results revealed that nimesulide (3), a non-steroidal anti-inflammatory drug, possesses a good anti-glycation activity in in-vitro BSA-MG and BSA-glucose glycation models with IC50 values of 330.56 ± 2.90, and 145.46 ± 16.35 µM, respectively. Phloroglucinol dihydrate (11), a drug used for the treatment of gastrointestinal diseases, showed a weak activity in BSA-MG glycation model (IC50 = 654.89 ± 2.50 µM), while it showed a good activity in BSA-glucose assay (IC50 = 148.23 ± 0.15 µM). Trimethylphloroglucinol (9), a drug used for the treatment of pain related to functional disorders of the digestive and biliary tracts, also showed a good antiglycation activity in BSA-MG model (IC50 = 321.15 ± 1.26 µM), while it was found to be inactive in in-vitro BSA-glucose assay (IC50 = 12.95% inhibition). These activities of drugs were compared with the anti-glycation activity of the standard, rutin (IC50 = 294.5 ± 1.50 µM in BSA-MG glycation model, and IC50 = 86.94 ± 0.24 µM in BSA- glucose model). Rest of the drugs exhibited a relatively weak antiglycation activity. This study identifies nimesulide (3), and phloroglucinol dihydrate (11) as new inhibitors of in-vitro protein glycation for further investigations as potential anti-diabetic agents.


Assuntos
Reposicionamento de Medicamentos , Glucose/metabolismo , Humanos , Técnicas In Vitro
5.
Cell Biol Int ; 42(4): 443-456, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29227005

RESUMO

Diabetes is associated with metabolic and functional alterations in the gut. Using an experimental model of streptozotocin (STZ)-induced diabetes in rodents, we analyzed the extracellular matrix (ECM) and TGF-ß/Smad signaling in the colon mucosa. Male rats were divided into normal control, diabetic and insulin treated diabetic groups during 4 and 9 weeks. Sirius red staining showed marked increase in the extracellular matrix deposition in diabetic mucosa. High levels of fibrillar collagen (I and III) and fibronectin mRNAs were also detected with an imbalance between MMPs/TIMPs activities. Moreover, an increased mesenchymal cell proliferation together with an enhanced expression of myofibroblasts markers vimentin and α-SMA were observed. TGF-ß/Smad signaling-related genes were determined using RT-PCR, Western blotting, and immunohistochemistry. Diabetic rats showed a significant up-regulation of TGF-ß1, TGF-ß receptors and the effectors p-Smad2/3 in the mucosa compared with control rats. Insulin treatment attenuated the stimulating effect of diabetes on colon ECM deposition and TGF-ß/Smad signaling. In conclusion, the overall results showed a deregulation of the TGFß1 pathway associated with the appearance of myofibroblasts and the accumulation of ECM in the mucosa of diabetic colon. These data provide the first in vivo evidence that TGF-ß1/Smad is a key component of intestinal tissue remodeling in diabetes.


Assuntos
Colo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Matriz Extracelular/metabolismo , Mucosa Intestinal/metabolismo , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Diabetes Mellitus Experimental/patologia , Colágenos Fibrilares/efeitos dos fármacos , Fibronectinas/metabolismo , Masculino , Miofibroblastos/metabolismo , Ratos , Ratos Wistar , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
J Appl Toxicol ; 36(11): 1516-25, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27062070

RESUMO

Smallanthus macroscyphus is an herb native to South America whose leaves are a source of antidiabetic compounds, although complete information about their safe use is not available yet. This study was developed to evaluate the toxicity profile of both 10% decoction and the sesquiterpene lactone polymatin A from S. macroscyphus leaves through in vitro cytotoxicity assays and in vivo subchronic oral toxicity. Cell viability of Hep-G2, COS1, CHO-K1 and Vero cell lines decreased in a concentration-dependent manner when cells were incubated with 0.4-200 µg ml(-1) of dry extract or 0.12-60 µg ml(-1) of polymatin A. In subchronic studies, decoction was orally administered to Wistar rats for 90 days at daily doses of 70, 140 and 280 mg kg(-1) of dry extract, whereas polymatin A was administered in the same way at doses of 7, 14 and 28 mg kg(-1) . No toxicity signs or deaths were observed. There were no changes in the behavior, body or organ weights, hematological, biochemical or urine parameters of the rats. No histopathological lesions were observed in the examined organs. The results indicate that the 10% decoction and polymatin A from S. macroscyphus leaves may be considered as non-toxic substances at a wide range of doses, including the effective hypoglycemic dose. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Asteraceae/química , Hipoglicemiantes/toxicidade , Lactonas/toxicidade , Extratos Vegetais/toxicidade , Folhas de Planta/química , Sesquiterpenos/toxicidade , Administração Oral , Animais , Asteraceae/crescimento & desenvolvimento , Células CHO , Células COS , Chlorocebus aethiops , Cricetulus , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Hipoglicemiantes/isolamento & purificação , Lactonas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta/crescimento & desenvolvimento , Ratos Wistar , Sesquiterpenos/isolamento & purificação , Testes de Toxicidade Subcrônica , Células Vero
8.
Pharm Biol ; 53(8): 1183-93, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25853966

RESUMO

CONTEXT: Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson, Asteraceae (yacon) roots are a natural product recognized by the traditional medicine to treat diabetes-related problems. There are no reports concerning the potential of yacon roots to reduce oxidative stress and ameliorate diabetes complications in diabetic animals. OBJECTIVE: This work analyzes the in vivo antioxidant activity and beneficial effects of yacon roots, using a model of streptozotocin-induced diabetes in rats. MATERIALS AND METHODS: Lipid peroxidation and other indicators of oxidative stress were determined in liver and kidney homogenates from non-diabetic rats, untreated diabetic rats, and diabetic rats treated orally with yacon flour (340 mg fructooligosaccharide/kg/d) as a diet supplement for 90 d. Biochemical parameters were determined in liver, kidney, and blood at the end of the experimental period. RESULTS: Yacon supplementation to diabetic rats produced a significant decrease in malondialdehyde levels in both liver (-30.97%) and kidney (-19.15%). Hepatic superoxide dismutase and catalase activities were significantly lower in diabetic-treated rats (-13.46 and -64.33%, respectively) compared with diabetic controls. Similar results were observed in kidney. The treatment of diabetic rats produced an increase of glutathione peroxidase and glutathione levels in liver (172.50 and 35.91%, respectively) and kidney (177.78 and 57.76%, respectively). Plasma cholesterol and triacylglycerol levels and liver fatty acid composition, which were altered in diabetic rats, reverted back to nearly normal with yacon treatment. CONCLUSIONS: These results indicate that yacon root flour is a potential diet supplement with high in vivo antioxidant activity.


Assuntos
Antioxidantes/uso terapêutico , Asteraceae , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Masculino , Estresse Oxidativo/fisiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
9.
J Appl Toxicol ; 34(12): 1320-31, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25493318

RESUMO

Lead is an important heavy metal pollutant in the environment. The nervous system, kidney and liver are the most susceptible organs to lead deposition, showing that this pollutant has no single target system. To examine the cellular and molecular mechanisms involved in their pathobiology of chronic lead at low-dose exposure in the liver, male Wistar rats were exposed to 0.06% lead acetate in drinking water every day for 4 months. At the end of the study, hepatic metal accumulation, morphology and function were examined. Immunochemical staining and Western blot analysis were performed to detect extracellular matrix proteins, α-smooth muscle actin and transforming growth factor (TGF)ß1/Smad pathway expression. Results showed increased laminin, collagen IV and fibronectin, located at the perisinusoidal space. Phenotypic transformation of hepatic stellate cells into myofibroblast-like cells was evidenced at the ultrastructural level and a significant expression of α-smooth muscle actin in Disse's space was observed. These findings were associated with a marked increase in TGFß1/Smad2/3 signaling. Our data suggest that, chronically, exposure to low levels of lead could trigger the onset of a hepatic fibrogenic process through upregulated TGFß1/Smad signaling.


Assuntos
Poluentes Ambientais/toxicidade , Chumbo/toxicidade , Cirrose Hepática/induzido quimicamente , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Animais , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Cirrose Hepática/urina , Masculino , Microscopia Eletrônica de Transmissão , Ratos Wistar , Fatores de Tempo
10.
Chem Biol Interact ; 209: 35-47, 2014 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-24309157

RESUMO

The aim of the present study was to analyze the in vivo hypoglycaemic effects of both decoction of Smallanthus macroscyphus leaves and pure crystalline polymatin A isolated from its leaves. Phytochemical analysis of the leaf decoction showed that its major constituents were caffeic, chlorogenic and three dicaffeoilquinic acids, together with the sesquiterpene lactone polymatin A. Oral glucose tolerance test in normal rats was performed to evaluate the hypoglycemic activity and to choose the minimum effective dose of the decoction and polymatin A. They have effective hypoglycemic activity at the minimum dose of 140 mg dry extract and 14 mg crystalline powder/kg body weight, respectively, and were selected for the following experiments. Oral administration of a single-dose of decoction produced a moderate lowering effect in fasting glycemia of normal rats, whereas polymatin A had no significant effect. We also assessed the effect of a single-dose on post-prandial blood glucose, resulting in an inhibition of the hyperglycemic peak after sucrose overload. Daily administration of decoction or polymatin A for 4 weeks produced an effective glycemic control in diabetic animals, with a decrease in urinary glucose excretion and a significant reduction in the HbA1c levels. Although there were no significant increases in plasma insulin levels, both treatments improved the fasting blood glucose/insulin ratio. In vivo acute toxicity studies were performed in adult Wistar rats. There were no deaths or signs of toxicity observed after oral administration of decoction or polymatin A at any dose level up to the highest dose tested (14.0 and 2.8 g/kg, respectively). The results presented here strongly support the notion that S. macroscyphus represents a new source of antidiabetic compounds that could help to manage diabetes more efficiently and safely.


Assuntos
Asteraceae/química , Glicemia/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Lactonas/farmacologia , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Administração Oral , Animais , Glicemia/análise , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/tratamento farmacológico , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Hipoglicemiantes/química , Lactonas/química , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Ratos , Ratos Wistar , Sesquiterpenos/química
11.
Dev Dyn ; 242(5): 572-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23401059

RESUMO

BACKGROUND: The axial skeleton develops from the sclerotome, a mesenchymal cell population derived from somites. Sclerotomal cells migrate from somites to the perinotochordal and perineural space where they differentiate into chondrocytes to form cartilage and bone. In anurans, little is known about the way how the sclerotome changes as development proceeds and how these events are regulated at the molecular level. Pax1, Pax9, and Uncx4.1 genes play a central role in the morphogenesis of the axial skeleton in vertebrates, regulating cell proliferation and chondrogenic specification of the sclerotome. RESULTS: In this work, we cloned and examined through whole-mount in situ hybridization and reverse transcriptase-polymerase chain reaction the expression patterns of pax1, pax9, and uncx transcription factors in the anuran Xenopus laevis. CONCLUSIONS: We found that these genes are similarly expressed in the sclerotome and in the pharyngeal pouch. A detailed analysis of the location of these transcripts showed that they are expressed in different subdomains of the sclerotomal compartment and differ from that observed in other vertebrates.


Assuntos
Desenvolvimento Embrionário/genética , Fator de Transcrição PAX9/genética , Fatores de Transcrição Box Pareados/genética , Xenopus laevis , Sequência de Aminoácidos , Animais , Desenvolvimento Ósseo/genética , Condrócitos/metabolismo , Condrócitos/fisiologia , Clonagem Molecular , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Hibridização In Situ , Dados de Sequência Molecular , Fator de Transcrição PAX9/metabolismo , Fatores de Transcrição Box Pareados/metabolismo , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Homologia de Sequência de Aminoácidos , Somitos/metabolismo , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Xenopus laevis/genética , Xenopus laevis/metabolismo
12.
Toxicol Appl Pharmacol ; 265(3): 380-9, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22995158

RESUMO

Cd exposure has been associated to an augmented risk for cardiovascular disease. We investigated the effects of 15 and 100 ppm of Cd on redox status as well as histological changes in the rat heart and the putative protective effect of a soy-based diet. Male Wistar rats were separated into 6 groups and treated during 60 days as follows: groups (1), (2) and (3) were fed a casein-based diet; groups (4), (5) and (6), a soy-based diet; (1) and (4) were given tap water; (2) and (5) tap water containing 15 ppm of Cd²âº; and (3) and (6) tap water containing 100 ppm of Cd²âº. Serum lipid peroxides increased and PON-1 activity decreased in group (3). Lipoperoxidation also increased in the heart of all intoxicated groups; however protein oxidation only augmented in (3) and reduced glutathione levels diminished in (2) and (3). Catalase activity increased in groups (3) and (6) while superoxide dismutase activity increased only in (6). Glutathione peroxidase activity decreased in groups (3) and (6). Nrf2 expression was higher in groups (3) and (6), and MTI expression augmented in (3). Histological examination of the heart tissue showed the development of hypertrophic and fusion of cardiomyocytes along with foci of myocardial fiber necrosis. The transmission electron microscopy analysis showed profound ultra-structural damages. No protection against tissue degeneration was observed in animals fed the soy-based diet. Our findings indicate that even though the intake of a soy-based diet is capable of ameliorating Cd induced oxidative stress, it failed in preventing cardiac damage.


Assuntos
Cádmio/toxicidade , Coração/efeitos dos fármacos , Miocárdio/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Soja/metabolismo , Animais , Arildialquilfosfatase/metabolismo , Catalase/metabolismo , Glutationa/metabolismo , Histocitoquímica , Masculino , Microscopia Eletrônica de Transmissão , Miocárdio/ultraestrutura , Fator 2 Relacionado a NF-E2/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
13.
Food Chem Toxicol ; 50(5): 1704-15, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22406203

RESUMO

Nephropathy is the most common cause of morbidity and mortality in diabetic patients. Prevention of this complication has a major relevance. Smallanthus sonchifolius (yacon) leaves have been shown to ameliorate hyperglycemia in streptozotocin-induced diabetic rats. We examined the beneficial effects of yacon leaves decoction on diabetic nephropathy and explored the possible underlying action mechanism. Streptozotocin-diabetic rats were orally administered 10% yacon leaves water decoction (70mg dry extract/kg body weight) once a day for 4weeks. Biochemical parameters in blood and urine were analyzed and immunohistochemistry staining, western immunoblotting and qRT-PCR were assessed. Yacon decoction significantly decreased high blood glucose level in diabetic rats and improved insulin production. Diabetic-dependent alterations in urinary albumin excretion, creatinine clearance, kidney hypertrophy and basement membrane thickening were attenuated by yacon decoction. These findings were associated with a marked decrease in TGF-ß1/Smad2/3 signaling. The expression of molecular markers of diabetic nephropathy such as collagen IV, laminin-1, fibronectin and collagen III were also diminished in the yacon-treated group compared to control diabetic group. These results suggest that yacon leaves decoction is a protective agent against renal damage in diabetic nephropathy, whose action can be mediated by TGF-ß/Smads signals.


Assuntos
Asteraceae/química , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Actinas/metabolismo , Animais , Western Blotting , Colágeno Tipo III/metabolismo , Colágeno Tipo IV/metabolismo , Nefropatias Diabéticas/fisiopatologia , Fibronectinas/metabolismo , Imuno-Histoquímica , Rim/metabolismo , Rim/fisiopatologia , Laminina/metabolismo , Masculino , Ratos , Ratos Wistar , Estreptozocina
14.
Dev Dyn ; 241(2): 257-69, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22170861

RESUMO

BACKGROUND: It has been established in several models that the p63 gene has an important role in the development of the epidermis and its derivatives. In Xenopus, only the ΔNp63 isoform of this gene has been cloned and its role during epidermal development remains unknown. RESULTS: In this work, we showed that ΔNp63 is expressed in the nonneural ectoderm since the gastrula stage and that it is regulated by the bone morphogenetic protein 4 (BMP4) signaling pathway. Our in vivo and in vitro experiments demonstrated that ΔNp63 is required in the earliest inductive steps of epidermal development. The overexpression of ΔNp63 caused an increase in epidermal markers with a suppression of neural induction while the blocking of ΔNp63 led to the opposite results. Finally, we found that ΔNp63 acts as an anti-apoptotic gene, regulating the transcription of some apoptotic and anti-apoptotic factors. CONCLUSION: The results suggest that ΔNp63 is an essential gene in early epidermal specification under the control of BMP4.


Assuntos
Proteína Morfogenética Óssea 4/metabolismo , Epiderme/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Fosfoproteínas/genética , Transativadores/genética , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologia , Animais , Apoptose/genética , Epiderme/metabolismo , Transdução de Sinais , Xenopus laevis/metabolismo
15.
Chem Biol Interact ; 194(1): 31-9, 2011 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-21907189

RESUMO

Fructooligosaccharides (FOS) are sugars found naturally at high concentrations in the storage roots of yacon. This study was designed to analyze the beneficial effects of subchronic oral consumption of yacon root flour as a diet supplement in Streptozotocin-induced diabetic Wistar rats. The experiments were carried out using yacon flour tablets containing the desired level of FOS (340 or 6800mg FOS/kg body weight/day). Yacon flour is a natural product obtained by a simple process of dehydration of yacon roots without added preservatives or chemicals. The administration of FOS-rich yacon flour to diabetic rats for 90days did not significantly alter the body weight of animals throughout the experimental period. Interestingly, a significant decrease in fasting plasma triacylglycerol and very low-density lipoprotein levels were observed. In addition, the treatment was able to protect the diabetic rats of the postprandial peak of plasma triacylglycerol. Yacon-supplemented rats showed an increased insulin-positive pancreatic cell mass distributed in small cell clusters within the exocrine parenchyma, but can only observe a slight increase in fasting plasma insulin levels. Glucagon like peptide-1 content in the cecum was significantly higher in diabetic rats treated with a diet supplemented with yacon flour compared with untreated diabetic animals, accompanied by an important cecal tissue enlargement. All these findings lead us to suggest that this incretin could be an effective mediator of the lipid lowering effects of FOS present in yacon flour. In conclusion, yacon root flour is a natural product rich in FOS that could be well positioned as a nutraceutical product since the present results demonstrate its beneficial effects on diabetes-associated hyperlipidemia.


Assuntos
Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Oligossacarídeos/uso terapêutico , Raízes de Plantas/química , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Peptídeo 1 Semelhante ao Glucagon/sangue , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Insulina/sangue , Lipoproteínas VLDL/sangue , Masculino , Oligossacarídeos/química , Oligossacarídeos/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo , Triglicerídeos/sangue
16.
Auton Neurosci ; 164(1-2): 51-61, 2011 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-21737358

RESUMO

Bone morphogenetic proteins (BMPs) are critical molecules during gut morphogenesis. However, little is known about their participation in the homeostasis of adult gut and their possible role in diseases. Gastrointestinal complications occur during diabetes with loss of enteric neurons. In this study, we investigated the possible involvement of BMPs signaling pathway in diabetic enteric neuropathy in an experimental model of diabetes in rats. The expression of BMPs, BMPs receptors and intracellular Smad effectors were assessed in control and diabetic smooth muscle layer of jejunum by immunofluorescence, Western blot and RT-PCR methods. Myenteric neurons and glial cells were measured by immunofluorescence using specific markers. In addition, cell apoptosis was evaluated by means of direct and indirect techniques. We demonstrated that diabetic ganglia displayed a significant decrease in ganglion size due to enhanced apoptosis and loss of peripherin. A decrease in glial fibrillary acidic protein (GFAP protein) was also observed in enteric glial cells. BMP-2 was down-regulated in the myenteric plexus of diabetic rats at 3 and 9weeks. A loss of enteric neurons by apoptosis was correlated with an ectopic BMP-4, increased BMPR-Ia and nuclear p-Smad1 expression in the myenteric plexus. Insulin-treatment prevented the intestinal alterations observed. These findings suggest that diabetes is associated with an abnormal BMP/Smad signaling expression in the myenteric ganglia that affects the homeostasis of the enteric plexus.


Assuntos
Proteína Morfogenética Óssea 2/deficiência , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/fisiopatologia , Plexo Mientérico/patologia , Plexo Mientérico/fisiopatologia , Proteína Smad1/deficiência , Animais , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/fisiologia , Neuropatias Diabéticas/metabolismo , Modelos Animais de Doenças , Homeostase/genética , Masculino , Plexo Mientérico/metabolismo , Ratos , Ratos Wistar , Proteína Smad1/genética , Proteína Smad1/fisiologia
17.
Chem Biol Interact ; 185(2): 143-52, 2010 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-20211156

RESUMO

The aim of the present study was to determine the in vivo hypoglycemic activity of five organic extracts and enhydrin obtained from yacon leaves. The main constituents of the most active fraction were identified. Five organic extracts and pure crystalline enhydrin were administered to normoglycemic, transiently hyperglycemic and streptozotocin (STZ)-diabetic rats. The fasting and post-prandial blood glucose, and serum insulin levels were estimated and an oral glucose tolerance test (OGTT) was performed for the evaluation of hypoglycemic activity and dose optimization of each extract. We found that the methanol, butanol and chloroform extracts showed effective hypoglycemic activity at minimum doses of 50, 10 and 20mg/kg body weight, respectively, and were selected for further experiments. Oral administration of a single-dose of each extract produced a slight lowering effect in the fasting blood glucose level of normal healthy rats, whereas each extract tempered significantly the hyperglycemic peak after food ingestion. Daily administration of each extract for 8 weeks produced an effective glycemic control in diabetic animals with an increase in the plasma insulin level. Phytochemical analysis of the most active fraction, the butanol extract, showed that caffeic, chlorogenic and three dicaffeoilquinic acids were significant components. Additionally, enhydrin, the major sesquiterpene lactone of yacon leaves, was also effective to reduce post-prandial glucose and useful in the treatment of diabetic animals (minimum dose: 0.8mg/kg body weight). The results presented here strongly support the notion that the phenolic compounds above as well as enhydrin are important hypoglycemic principles of yacon leaves that could ameliorate the diabetic state.


Assuntos
Asteraceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Extratos Vegetais/farmacologia , Folhas de Planta/química , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Ácido Clorogênico/química , Ácido Clorogênico/classificação , Ácido Clorogênico/farmacologia , Ácido Clorogênico/uso terapêutico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Relação Dose-Resposta a Droga , Teste de Tolerância a Glucose , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Insulina/sangue , Masculino , Extratos Vegetais/química , Extratos Vegetais/uso terapêutico , Ratos , Ratos Wistar , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Solventes/química , Estreptozocina/toxicidade , Fatores de Tempo
18.
J Appl Toxicol ; 29(3): 214-22, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18989869

RESUMO

Vitamin A is an essential lipid-soluble nutrient that is crucial for morphogenesis and adult tissue maintenance. The retinoid homeostasis in the liver depends on a regular supply of vitamin A from an adequate dietary intake to preserve the normal organ structure and functions. This study focuses on the effect of vitamin A deficiency on the morphology and extracellular proteins expression of the liver in adult Wistar rats. Animals were fed with a normal (control group) or deficient vitamin A diet for 3 months. At the end of the experimental period, histological examination of the livers under light and electron microscopy revealed that vitamin A deficiency produced a loss of hepatocyte cord disposition with an irregular parenchymal organization. Abundant fat droplets were present in the cytoplasm of the hepatocytes. Elongated myofibroblastic-like cells with an irregular cytoplasmic process and without lipid droplets could be seen at the perisinusoidal space, where an elevated intensity of alpha smooth muscle actin (alpha-SMA) was observed. These results suggest that an activation of hepatic stellate cells (HSCs) occurred. Moreover, immunochemical methods revealed that vitamin A deficiency led to an increased expression of hepatic fibronectin, laminin and collagen type IV. We propose that vitamin A deprivation caused liver injury and that HSCs underwent a process of activation in which they produced alpha-SMA and synthesized extracellular components. These changes may be a factor predisposing to liver fibrosis. In consequence, vitamin A deprivation could affect human and animal health.


Assuntos
Matriz Extracelular/metabolismo , Hepatócitos/patologia , Fígado/metabolismo , Fígado/patologia , Deficiência de Vitamina A/patologia , Actinas/metabolismo , Actinas/ultraestrutura , Animais , Colágeno Tipo IV/metabolismo , Colágeno Tipo IV/ultraestrutura , Matriz Extracelular/ultraestrutura , Feminino , Fibronectinas/metabolismo , Fibronectinas/ultraestrutura , Fibrose/patologia , Hepatócitos/ultraestrutura , Imuno-Histoquímica , Laminina/metabolismo , Laminina/ultraestrutura , Fígado/ultraestrutura , Distribuição Aleatória , Ratos , Ratos Wistar
19.
Dev Biol ; 323(1): 114-29, 2008 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-18775422

RESUMO

The neural crest is induced at the border of the neural plate in a multistep process by signals emanated from the epidermis, neural plate and mesoderm. In this work we show for the first time the existence of a neural crest maintenance step which is dependent on signals released from the mesoderm. We identified Endothelin-1 (Edn1) and its receptor (Ednra) as key players of this signal and we show that Edn1/Ednra signaling is required for maintenance of the neural crest by a dual mechanism of cell specification and cell survival. We show that: (i) Ednra is expressed in prospective neural crest; (ii) loss-of-function experiments with antisense morpholino or with specific chemical inhibitor suppress the expression of early neural crest markers; (iii) gain-of-function experiments expand the neural crest territory; (iv) epistatic experiments show that Ednra/Edn1 is downstream of the early neural crest gene Msx1 and upstream of the late genes Sox9 and Sox10; and (v) Edn1/Ednra signaling inhibits apoptosis and controls cell specification of the neural crest. Together, our results provide insight on a new role of Edn1/Ednra cell signaling pathway during early neural crest development.


Assuntos
Indução Embrionária/genética , Endotelina-1/metabolismo , Crista Neural/fisiologia , Receptor de Endotelina A/metabolismo , Transdução de Sinais/fisiologia , Animais , Embrião não Mamífero/metabolismo , Embrião não Mamífero/fisiologia , Endotelina-1/genética , Imuno-Histoquímica , Hibridização In Situ , Modelos Biológicos , Crista Neural/metabolismo , Receptor de Endotelina A/genética , Transdução de Sinais/genética , Xenopus/embriologia , Xenopus/genética , Xenopus/metabolismo
20.
Dev Dyn ; 237(1): 112-23, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18095347

RESUMO

Gangliosides are a subfamily of complex glycosphingolipids (GSLs) with important roles in many biological processes. In this study, we report the cDNA cloning, functional characterization, and the spatial and temporal expression of Xlcgt and Xlgd3 synthase during Xenopus laevis development. Xlcgt was expressed both maternally and zigotically persisting at least until stage 35. Maternal Xlgd3 synthase mRNA could not be detected and showed a steady-state expression from gastrula to late tailbud stage. Xlcgt is mainly present in involuted paraxial mesoderm, neural folds, and their derivatives. Xlgd3 synthase transcripts were detected in the dorsal blastoporal lip, in the presumptive neuroectoderm, and later in the head region, branchial arches, otic and optic primordia. We determined the effect of glycosphingolipid depletion with 1-phenyl-2-palmitoyl-3-morpholino-1-propanol (PPMP) in mesodermal layer. PPMP-injected embryos showed altered expression domains in the mesodermal markers. Our results suggest that GSL are involved in convergent-extension movements during early development in Xenopus.


Assuntos
Enzimas/metabolismo , Glicoesfingolipídeos/biossíntese , Proteínas de Xenopus/metabolismo , Xenopus laevis/metabolismo , Sequência de Aminoácidos , Animais , Western Blotting , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , Embrião não Mamífero/metabolismo , Ativação Enzimática/efeitos dos fármacos , Enzimas/genética , Regulação da Expressão Gênica no Desenvolvimento , Regulação Enzimológica da Expressão Gênica , Glucosiltransferases/classificação , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Hibridização In Situ , Microscopia Confocal , Dados de Sequência Molecular , Morfolinas/farmacologia , Filogenia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Sialiltransferases/classificação , Sialiltransferases/genética , Sialiltransferases/metabolismo , Esfingolipídeos/farmacologia , Proteínas de Xenopus/genética , Xenopus laevis/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...