204 research outputs found

    DJ-1 contributes to adipogenesis and obesity-induced inflammation

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    Adipose tissue functions as an endocrine organ, and the development of systemic inflammation in adipose tissue is closely associated with metabolic diseases, such as obesity and insulin resistance. Accordingly, the fine regulation of the inflammatory response caused by obesity has therapeutic potential for the treatment of metabolic syndrome. In this study, we analyzed the role of DJ-1 (PARK7) in adipogenesis and inflammation related to obesity in vitro and in vivo. Many intracellular functions of DJ-1, including oxidative stress regulation, are known. However, the possibility of DJ-1 involvement in metabolic disease is largely unknown. Our results suggest that DJ-1 deficiency results in reduced adipogenesis and the down-regulation of pro-inflammatory cytokines in vitro. Furthermore, DJ-1-deficient mice show a low-level inflammatory response in the high-fat diet-induced obesity model. These results indicate previously unknown functions of DJ-1 in metabolism and therefore suggest that precise regulation of DJ-1 in adipose tissue might have a therapeutic advantage for metabolic disease treatment.open0

    A Toll-Like Receptor 2 Pathway Regulates the Ppargc1a/b Metabolic Co-Activators in Mice with Staphylococcal aureus Sepsis

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    Activation of the host antibacterial defenses by the toll-like receptors (TLR) also selectively activates energy-sensing and metabolic pathways, but the mechanisms are poorly understood. This includes the metabolic and mitochondrial biogenesis master co-activators, Ppargc1a (PGC-1α) and Ppargc1b (PGC-1β) in Staphylococcus aureus (S. aureus) sepsis. The expression of these genes in the liver is markedly attenuated inTLR2−/− mice and markedly accentuated in TLR4−/− mice compared with wild type (WT) mice. We sought to explain this difference by using specific TLR-pathway knockout mice to test the hypothesis that these co-activator genes are directly regulated through TLR2 signaling. By comparing their responses to S. aureus with WT mice, we found that MyD88-deficient and MAL-deficient mice expressed hepatic Ppargc1a and Ppargc1b normally, but that neither gene was activated in TRAM-deficient mice. Ppargc1a/b activation did not require NF-kβ, but did require an interferon response factor (IRF), because neither gene was activated in IRF-3/7 double-knockout mice in sepsis, but both were activated normally in Unc93b1-deficient (3d) mice. Nuclear IRF-7 levels in TLR2−/− and TLR4−/− mice decreased and increased respectively post-inoculation and IRF-7 DNA-binding at the Ppargc1a promoter was demonstrated by chromatin immunoprecipitation. Also, a TLR2-TLR4-TRAM native hepatic protein complex was detected by immunoprecipitation within 6 h of S. aureus inoculation that could support MyD88-independent signaling to Ppargc1a/b. Overall, these findings disclose a novel MyD88-independent pathway in S. aureus sepsis that links TLR2 and TLR4 signaling in innate immunity to Ppargc1a/b gene regulation in a critical metabolic organ, the liver, by means of TRAM, TRIF, and IRF-7

    Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis

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    DJ-1 is a novel oncogene and also causative gene for familial Parkinson’s disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene

    Deficiências minerais em plantas de bertalha ( Basella alba, L.)

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    Basella alba is used as a major food on the Amazon region, north Brazil for its high mineral and vitamins content. The purpose of the present work was: a) obtain a clear picture of the macronutrient deficiency; b) growth of the plants in function of (1); c) analyptical levels found in the leaves. Young Basella alba plants (bertalha in Portuguese) were cultivated in pots containing fine pure quartz and irrigated by percolation with different nutrient solutions lacking one of the element at the time. Clear cut symptoms were obtained for all macronutrients. Only the omission of nitrogen and potassium affect the dry matter production of plants. The range in dry matter for unhealthy and healthy leaves were: N% = 1.25--3-55; P% = 0.17-0.36; K% = 0.46-3.55; Ca% = 0,62-1.78; Mg% = 0.37-0.80; S% = 0.19-0.13.Plantas de bertalha (Basella alba, L.) INPA-1 foram cultivadas em casa de vegetação em quartzo moído, irrigadas com soluções nutritivas conforme SARRUGE (1975) e submetidas aos seguintes tratamentos: completo, omissão de N, omissão de P, omissão de K, omissão de Ca, omissão de Mg e omissão de S, com o objetivo de: (a) obter sintomas de deficiência dos ma cronutrientes; (b) analisar o crescimento das plantas através da produção de matéria seca; (c) determinar a concentração dos macronutrientes nas folhas e caules das plantas cultivadas nos diversos tratamentos. Os sintomas visuais de deficiência foram identificados e descritos. As plantas foram coletadas e separadas em raiz, caule, folhas e determinaram-se os teores dos macronutrientes minerais neste material. Os resultados obtidos mostram: - os sintomas visuais de deficiência são bem definidos e de fácil caracterização para todos os nutrientes; - só foi possível detectar efeito na produção de matéria seca das folhas e caules para omissão de nitrogênio e para omissão de potássio nos caules; - os níveis de deficiência e adequação obtidos nas folhas foram respectivamente: N% = 1,25 e 2,63; P% = 0,17 e 0,36; K% = 0,46 e 3,55; Ca% = 0,62e 1,78; Mg% = 0,37 e 0,80; s%= 0,19 e 0,23. - os níveis de deficiência e adequação obtidos nos caules foram respectivamente: N% = 0,67 e 0,98; P% = 0,13 e 0,31; K% = 0,73 e 2,67; Ca% = 0,11 e 0,64; Mg% = 0,08 e 0,20; S% = 0,15 e 0,20

    Parkinson’s disease mouse models in translational research

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    Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

    Mineral nutrition of vegetable crops: XXV - Mineral nutrition of new zealand spinach plant (Tetragonia expansa Murr.)

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    The present work was carried out in order to study: a - the effect of omission and presence of the macronutrients and boron on the growth of the plants; b - deficiency symptoms of macronutrients, as well of boron; c - the effect of the deficiency of each nutrient on the chemical composition of the plants. Young spinach plants were grown in pots containing pure quartz sand. Several times a day the plants were irrigated by percolation with nutrient solutions. The treatments were: complete solution and deficient solution, in which each one of the macronutrients was omitted as well boron. Soon as the malnutrition symptoms appered, the plants were harvested and analysed chemically. - symptoms of malnutrition are easily observed for N, K, Ca and B. - symptoms of malnutrition for P, S and Mg are not easily identified. - the nutrient content, in dry matter, in deficient leaves and healthy leaves is:O trabalho teve como objetivo estudar alguns aspectos da nutrição mineral do espinafre (Tetragonia expansa Murr.) no que concerne: 1 - Efeitos da omissão dos macronutrientes e do boro, na obtenção de um quadro sintomatológico; 2 - Efeitos das carências na produção de matéria seca e composição química da planta. Mudas com trinta dias de idade foram transplantadas para soluções nutritivas carentes nos macronutrientes e/ou em boro. A coleta das plantas foi realizada quando os sintomas de deficiência se tornaram evidentes. No material seco procedeu-se a análise química. Os dados mostram que: 1 - os sintomas visuais de deficiência de N, K, Ca e B apresentam-se bem definidos; sendo que os de P, Mg e S são de difícil caracterização ; 2 - os teores dos nutrientes em plantas sadias e deficientes são
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