21 research outputs found

    Colonic Microbiota Profile Characterization of the Responsiveness to Dietary Fibre Treatment in Hypercholesterolemia

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    This study aimed to determine how the microbiota profile might be predisposed to a better response in blood lipid profiles due to dietary fibre supplementation. A three-arm intervention study that included three different fibre types (mainly insoluble, soluble, and antioxidant fibre) supplemented (19.2 g/day) during 2 months in individuals with hypercholesterolemia was developed. Changes in faecal microbiota and blood lipid profile after fibre supplementation were determined. In all volunteers, regardless of fibre type, an increase in the abundance of Bifidobacterium was observed, and similarly, an inverse relationship between faecal propionic acid and blood LDL-cholesterol, LDL particle size, and LDL/HDL particle ratio (p-values 0.0067, 0.0002, and 0.0067, respectively) was observed. However, not all volunteers presented an improvement in lipid profile. The non-responders to fibre treatment showed a decrease in microbiota diversity (Shannon and Simpson diversity index p-values of 0.0110 and 0.0255, respectively) after the intervention; where the reduction in short-chain fatty acids (SCFAs) producing bacterial genera such as Clostridium XIVa and Ruminococcus after dietary fibre treatment was the main difference. It was concluded that the non-responsiveness to dietary fibre treatment might be mediated by the lack of ability to maintain a stable SCFA producing bacteria diversity and composition after extra fibre intake.The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the Seventh Framework Programme of the European Union (FP7/2007-2013) under REA grant agreement no. 600388 (TECNIOspring Progamme) and from the Agency for Business Competitiveness of the Government of Catalonia ACCIÓ that support the fellowship given to Ana Belén Granado-Serrano (TECSPR14-0-0023

    Cell Stress Induces Mislocalization of Transcription Factors with Mitochondrial Enrichment

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    Previous evidence links the formation of extranuclear inclusions of transcription factors, such as ERK, Jun, TDP-43, and REST, with oxidative, endoplasmic-reticulum, proteasomal, and osmotic stress. To further characterize its extranuclear location, we performed a high-content screening based on confocal microscopy and automatized image analyses of an epithelial cell culture treated with hydrogen peroxide, thapsigargin, epoxomicin, or sorbitol at different concentrations and times to recreate the stresses mentioned above. We also performed a subcellular fractionation of the brain from transgenic mice overexpressing the Q331K-mutated TARDBP, and we analyzed the REST-regulated mRNAs. The results show that these nuclear proteins exhibit a mitochondrial location, together with significant nuclear/extranuclear ratio changes, in a protein and stress-specific manner. The presence of these proteins in enriched mitochondrial fractions in vivo confirmed the results of the image analyses. TDP-43 aggregation was associated with alterations in the mRNA levels of the REST target genes involved in calcium homeostasis, apoptosis, and metabolism. In conclusion, cell stress increased the mitochondrial translocation of nuclear proteins, increasing the chance of proteostasis alterations. Furthermore, TDP-43 aggregation impacts REST target genes, disclosing an exciting interaction between these two transcription factors in neurodegenerative processes

    Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS

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    Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a gender bias towards major prevalence in male individuals. Several data suggest the involvement of oxidative stress and mitochondrial dysfunction in its pathogenesis, though differences between genders have not been evaluated. For this reason, we analysed features of mitochondrial oxidative metabolism, as well as mitochondrial chain complex enzyme activities and protein expression, lipid profile, and protein oxidative stress markers, in the Cu,Zn superoxide dismutase with the G93A mutation (hSOD1-G93A)- transgenic mice and Neuro2A(N2A) cells overexpressing hSOD1-G93A. Results and Conclusions: Our results show that overexpression of hSOD1-G93A in transgenic mice decreased efficiency of mitochondrial oxidative phosphorylation, located at complex I, revealing a temporal delay in females with respect to males associated with a parallel increase in selected markers of protein oxidative damage. Further, females exhibit a fatty acid profile with higher levels of docosahexaenoic acid at 30 days. Mechanistic studies showed that hSOD1-G93A overexpression in N2A cells reduced complex I function, a defect prevented by 17βestradiol pretreatment. In conclusion, ALS-associated SOD1 mutation leads to delayed mitochondrial dysfunction in female mice in comparison with males, in part attributable to the higher oestrogen levels of the former. This study is important in the effort to further understanding of whether different degrees of spinal cord mitochondrial dysfunction could be disease modifiers in ALS

    Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS

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    Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a gender bias towards major prevalence in male individuals. Several data suggest the involvement of oxidative stress and mitochondrial dysfunction in its pathogenesis, though differences between genders have not been evaluated. For this reason, we analysed features of mitochondrial oxidative metabolism, as well as mitochondrial chain complex enzyme activities and protein expression, lipid profile, and protein oxidative stress markers, in the Cu,Zn superoxide dismutase with the G93A mutation (hSOD1-G93A)- transgenic mice and Neuro2A(N2A) cells overexpressing hSOD1-G93A. Results and Conclusions: Our results show that overexpression of hSOD1-G93A in transgenic mice decreased efficiency of mitochondrial oxidative phosphorylation, located at complex I, revealing a temporal delay in females with respect to males associated with a parallel increase in selected markers of protein oxidative damage. Further, females exhibit a fatty acid profile with higher levels of docosahexaenoic acid at 30 days. Mechanistic studies showed that hSOD1-G93A overexpression in N2A cells reduced complex I function, a defect prevented by 17β- estradiol pretreatment. In conclusion, ALS-associated SOD1 mutation leads to delayed mitochondrial dysfunction in female mice in comparison with males, in part attributable to the higher oestrogen levels of the former. This study is important in the effort to further understanding of whether different degrees of spinal cord mitochondrial dysfunction could be disease modifiers in ALS. Keywords: Motor neuron, Complex I, Respirometry, Fatty acid composition, Oxidative damage, EstrogensThis study was funded by the Spanish Ministry of Health, Institute Carlos III: FIS grants PI14/00757, PI14/00328, PI 14/01115. Financed by the European Union, program European Regional Development Fund “A way to build Europe”. Supported by the Generalitat de Catalunya (2014SGR168 and predoctoral fellows for OR-N and PT), by FUNDELA (C100013), “RedELA Investigación” platform and by the Fundació Miquel Valls (Jack Van den Hoek donation for ALS research

    Cryptic exon splicing function of TARDBP interacts with autophagy in nervous tissue

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    TARDBP (TAR DNA binding protein) is one of the components of neuronal aggregates in sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration. We have developed a simple quantitative method to evaluate TARDBP splicing function that was applied to spinal cord, brainstem, motor cortex, and occipital cortex in ALS (n=8) cases compared to age- and gender matched control (n=17). Then, we quantified the abundance of a TARDBP-spliced cryptic exon present in ATG4B (autophagy related 4B cysteine peptidase) mRNA. Results of these analyses demonstrated that the loss of this TARDBP function in spinal cord, brainstem, motor cortex, and occipital cortex differentiated ALS from controls (area under the curve of receiver operating characteristic: 0.85). Significant correlations were also observed between cryptic exon levels, age, disease duration, and aberrant mRNA levels. To test if TARDBP function in splicing is relevant in ATG4B major function (autophagy) we downregulated TARDBP expression in human neural tissue and in HeLa cells, demonstrating that TARDBP is required for maintaining the expression of ATG4B. Further, ATG4B overexpression alone is sufficient to completely prevent the increase of SQSTM1 induced by TARDBP downregulation in human neural tissue cells and in cell lines. In conclusion, the present findings demonstrate abnormal alternative splicing of ATG4B transcripts in ALS neural tissue in agreement with TARDBP loss of function, leading to impaired autophagy

    Estudio de los mecanismos de acción molecular de polifenoles de la dieta en cultivos celulares y animales de experimentación

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    En nuestro grupo de trabajo se ha puesto a punto un modelo de estrés oxidativo en células hepáticas (HepG2). Trabajos previos realizados en dicho modelo han demostrado un efecto protector de las concentraciones fisiológicas de los extractos polifenólicos de frutas y de los polifenoles puros. Cuando las dosis de estos compuestos fenólicos se incrementan, se produce el efecto contrario, la inducción de la apoptosis. Sin embargo, los procesos moleculares responsables de estos efectos aún no han sido analizados y constituyen el objetivo principal de este trabajo. En este sentido, la línea de hepatocarcinoma celular humano HepG2 permite valorar el potencial efecto anticancerígeno de los polifenoles de la dieta (quercetina) mediante el estudio de las señales moleculares que regulan la apoptosis, proliferación y supervivencia celular. Además, esta línea celular se considera uno de los modelos experimentales ex vivo que reproduce con mayor fidelidad al hepatocito humano, con lo que también permite evaluar el potencial efecto protector de los polifenoles de la dieta (epicatequina y ácido clorogénico). De manera similar, la puesta a punto de un modelo animal de daño oxidativo hepático posibilita valorar in vivo el potencial efecto protector de una dieta suplementada con un alimento rico en polifenoles (cacao). Con este fin, se plantean varios objetivos específicos. En primer lugar, estudiar el efecto directo de la quercetina en las células HepG2. Análisis de la modulación de proteínas clave en los procesos de proliferación/supervivencia y/o muerte celular. En segundo lugar, evaluar el efecto de la epicatequina y el ácido clorogénico en línea celular HepG2. Análisis del estado redox y de la señalización molecular relacionada con la proliferación, supervivencia y/o muerte celular. Y por último, determinar del potencial efecto protector de una dieta rica en cacao frente al daño oxidativo inducido por dietil-N-nitrosamina en el hígado de la rata. Valoración de los sistemas de defensa antioxidante y detoxificante e implicación de proteínas clave relacionadas con la proliferación, supervivencia y/o muerte celular

    Short-Term Panax Ginseng Extract Supplementation Reduces Fasting Blood Triacylglycerides and Oxygen Consumption during Sub-Maximal Aerobic Exercise in Male Recreational Athletes

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    Ginseng, a popular herbal supplement among athletes, is believed to enhance exercise capacity and performance. This study investigated the short-term effects of Panax ginseng extract (PG) on aerobic capacity, lipid profile, and cytokines. In a 14-day randomized, double-blind trial, male participants took 500 mg of PG daily. Two experiments were conducted: one in 10 km races (n = 31) and another in a laboratory-controlled aerobic capacity test (n = 20). Blood lipid and cytokine profile, ventilation, oxygen consumption, hemodynamic and fatigue parameters, and race time were evaluated. PG supplementation led to reduced total blood lipid levels, particularly in triacylglycerides (10 km races −7.5 mg/dL (95% CI −42 to 28); sub-maximal aerobic test −14.2 mg/dL (95% CI −52 to 23)), while post-exercise blood IL-10 levels were increased (10 km 34.0 pg/mL (95% CI −2.1 to 70.1); sub-maximal aerobic test 4.1 pg/mL (95% CI −2.8 to 11.0)), and oxygen consumption decreased during the sub-maximal aerobic test (VO2: −1.4 mL/min/kg (95% CI −5.8 to −0.6)). No significant differences were noted in race time, hemodynamic, or fatigue parameters. Overall, PG supplementation for 2 weeks showed benefits in blood lipid profile and energy consumption during exercise among recreational athletes. This suggests a potential role for PG in enhancing exercise performance and metabolic health in this population

    Characterization of the post-prandial insulinemic response and low glycaemic index of a soy beverage

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    Soybean is recognized as rich source of bioactive compounds for the improvement of glucose homeostasis. However, the post-prandial mechanisms of action have not been extensively described. The aim of this study is to determine the changes in glucose homeostasis and related factors after acute intake of a soy beverage. Twenty-nine subjects (15 women and 14 men, with an average age of 19.5 ± 1.2) ingested 500 mL of water, glucose (20.5 g/500 mL) and soy beverage (20 g of carbohydrate) in three separate sessions. Capillary blood glucose was monitored every 15 min until 120 min post-prandial, and blood samples were collected at baseline and after 60 min for insulin, incretin, free amino acids, antioxidant capacity and inflammation marker analysis. The increase in capillary glucose after soy-beverage intake was negligible. This is explained in part by an increase in 83% in insulin levels than induced with glucose alone, which is mainly mediated by a low insulin degradation ratio (determined by c-peptide ratio), incretins and likely also by the modulation of the antioxidant environment. No associations were observed between the insulin levels and soy amino acid uptake. It could be concluded that the acute low glycaemic response of a soy beverage may involves a relationship between incretin and insulin secretion and insulin degradation
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