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11.
Calderón-Sánchez EM Ruiz-Hurtado G Smani T Delgado C Benitah JP Gómez AM Ordóñez A 《Cell calcium》2011,50(1):84-90
Ischemia/reperfusion (I/R) damage in the heart occurs mainly during the first minutes of reperfusion. Urocortin (Ucn) is a member of the corticotrophin-releasing factor that has been identified as a potent endogenous cardioprotector peptide when used in pre- and postconditioning protocols. However, the underlying mechanisms are not completely elucidated. Here, we focused on intracellular calcium ([Ca2+]i) handling by Ucn when applied in early reperfusion. We used Langendorff-perfused rat hearts to determine hemodynamic parameters, and confocal microscopy to study global [Ca2+]i transients evoked by electrical stimulation in isolated cardiomyocytes loaded with fluorescence Ca2+ dye fluo-3AM. We found that the acute application of Ucn at the onset of reperfusion, in isolated hearts submitted to ischemia, fully recovered the hearts contractility and relaxation. In isolated cardiac myocytes, following ischemia we observed that the diastolic [Ca2+]i was increased, the systolic [Ca2+]i transients amplitude were depressed and sarcoplasmic reticulum (SR) Ca2+ load was reduced. These effects were correlated to a decrease in the Na+/Ca2+ exchanger (NCX) activity. Importantly, Ucn applied at reperfusion produced a complete recovery in diastolic [Ca2+]i and global [Ca2+]i transient amplitude, which were due to NCX activity improvement. In conclusion, we demonstrated that [Ca2+]i handling play an essential role in postconditioning action of Ucn. 相似文献
12.
González-Cabrera J Farinós GP Caccia S Díaz-Mendoza M Castañera P Leonardi MG Giordana B Ferré J 《Applied and environmental microbiology》2006,72(4):2594-2600
Sesamia nonagrioides is one of the most damaging pests of corn in Spain and other Mediterranean countries. Bt corn expressing the Bacillus thuringiensis Cry1Ab toxin is being grown on about 58,000 ha in Spain. Here we studied the mode of action of this Cry protein on S. nonagrioides (binding to specific receptors, stability of binding, and pore formation) and the modes of action of other Cry proteins that were found to be active in this work (Cry1Ac, Cry1Ca, and Cry1Fa). Binding assays were performed with (125)I- or biotin-labeled toxins and larval brush border membrane vesicles (BBMV). Competition experiments indicated that these toxins bind specifically and that Cry1Aa, Cry1Ab, and Cry1Ac share a binding site. Cry1Ca and Cry1Fa bind to different sites. In addition, Cry1Fa binds to Cry1A's binding site with very low affinity and vice versa. Binding of Cry1Ab and Cry1Ac was found to be stable over time, which indicates that the observed binding is irreversible. The pore-forming activity of Cry proteins on BBMV was determined using the voltage-sensitive fluorescent dye DiSC(3)(5). Membrane permeability increased in the presence of the active toxins Cry1Ab and Cry1Fa but not in the presence of the nonactive toxin Cry1Da. In terms of resistance management, based on our results and the fact that Cry1Ca is not toxic to Ostrinia nubilalis, we recommend pyramiding of Cry1Ab with Cry1Fa in the same Bt corn plant for better long-term control of corn borers. 相似文献
13.
Dhammika H. M. L. P. Navarathna Erica V. Stein Elizabeth C. Lessey-Morillon Debasis Nayak Gema Martin-Manso David D. Roberts 《PloS one》2015,10(5)
CD47 is a widely expressed receptor that regulates immunity by engaging its counter-receptor SIRPα on phagocytes and its secreted ligand thrombospondin-1. Mice lacking CD47 can exhibit enhanced or impaired host responses to bacterial pathogens, but its role in fungal immunity has not been examined. cd47-/- mice on a C57BL/6 background showed significantly increased morbidity and mortality following Candida albicans infection when compared with wild-type mice. Despite normal fungal colonization at earlier times, cd47-/- mice at four days post-infection had increased colonization of brain and kidneys accompanied by stronger inflammatory reactions. Neutrophil and macrophage numbers were significantly elevated in kidneys and neutrophils in the brains of infected cd47-/- mice. However, no defect in phagocytic activity towards C. albicans was observed in cd47-/- bone-marrow-derived macrophages, and neutrophil and macrophage killing of C. albicans was not impaired. CD47-deficiency did not alter the early humoral immune response to C. albicans. Th1, Th2, and Th17 population of CD4+ T cells were expanded in the spleen, and gene expression profiles of spleen and kidney showed stronger pro-inflammatory signaling in infected cd47-/- mice. The chemoattractant chemokines MIP-2α and MIP-2β were highly expressed in infected spleens of cd47-/- mice. G-CSF, GM-CSF, and the inflammasome component NLRP3 were more highly expressed in infected cd47-/- kidneys than in infected wild-type controls. Circulating pro- (TNF-α, IL-6) and anti-inflammatory cytokines (IL-10) were significantly elevated, but IL-17 was decreased. These data indicate that CD47 plays protective roles against disseminated candidiasis and alters pro-inflammatory and immunosuppressive pathways known to regulate innate and T cell immunity. 相似文献
14.
Victoria Catalán Javier Gómez-Ambrosi Amaia Rodríguez Beatriz Ramírez Víctor Valentí Rafael Moncada Camilo Silva Javier Salvador Gema Frühbeck 《Genes & nutrition》2015,10(3)
Inflammation is a critical contributor to the pathogenesis of metabolic disorders with adipose tissue being crucial in the inflammatory response by releasing multiple adipokines with either pro- or anti-inflammatory activities with potential functions as metabolic regulators. Peripheral blood mononuclear cells (PBMC) have been proposed as representative of the inflammatory status in obesity. The aim of the present study was to evaluate the contribution of PBMC to the obesity-associated chronic inflammation analyzing the expression of novel adipokines. Samples obtained from 69 subjects were used in the study. Real-time PCR determinations were performed to quantify gene expression levels in PBMC of novel adipokines including chemerin, chitinase-3-like protein 1 (YKL-40), lipocalin-2 (LCN-2) and osteopontin (OPN), and their circulating concentrations were also determined by ELISA. We show, for the first time, that PBMC gene expression levels of chemerin (P < 0.0001), chitinase-3-like protein 1 (P = 0.010), lipocalin-2 (P < 0.0001) and osteopontin (P < 0.0001) were strongly upregulated in obesity independently of the glycemic state. Circulating concentrations of these adipokines followed the same trend being significantly higher (P < 0.05) in obese normoglycemic and type 2 diabetic patients compared to lean volunteers and also associated (P < 0.05) with their corresponding mRNA levels in PBMC. These results provide evidence that alterations in inflammation-related adipokines are manifest in PBMC, which might contribute to the low-grade chronic inflammation that characterizes obesity.
Electronic supplementary material
The online version of this article (doi:10.1007/s12263-015-0460-8) contains supplementary material, which is available to authorized users. 相似文献15.
Ramírez-Salinas Gema L. García-Machorro J. Quiliano Miguel Zimic Mirko Briz Verónica Rojas-Hernández Saul Correa-Basurto J. 《Journal of molecular modeling》2015,21(11):1-14
Journal of Molecular Modeling - There is a wide variety of ion channel types with various types of blockers, making research in this field very complicated. To reduce this complexity, it is... 相似文献
16.
Ana B. Fagundo Susana Jiménez-Murcia Cristina Giner-Bartolomé Mohammed Anisul Islam Rafael de la Torre Antoni Pastor Felipe F. Casanueva Ana B. Crujeiras Roser Granero Rosa Ba?os Cristina Botella Jose M. Fernández-Real Gema Frühbeck Javier Gómez-Ambrosi José M. Menchón Francisco J. Tinahones Fernando Fernández-Aranda 《PloS one》2015,10(6)
The prefrontal (PFC) and orbitofrontal cortex (OFC) appear to be associated with both executive functions and olfaction. However, there is little data relating olfactory processing and executive functions in humans. The present study aimed at exploring the role of olfaction on executive functioning, making a distinction between primary and more cognitive aspects of olfaction. Three executive tasks of similar difficulty were used. One was used to assess hot executive functions (Iowa Gambling Task-IGT), and two as a measure of cold executive functioning (Stroop Colour and Word Test-SCWT and Wisconsin Card Sorting Test-WCST). Sixty two healthy participants were included: 31 with normosmia and 31 with hyposmia. Olfactory abilities were assessed using the ‘‘Sniffin’ Sticks’’ test and the olfactory threshold, odour discrimination and odour identification measures were obtained. All participants were female, aged between 18 and 60. Results showed that participants with hyposmia displayed worse performance in decision making (IGT; Cohen’s-d = 0.91) and cognitive flexibility (WCST; Cohen’s-d between 0.54 and 0.68) compared to those with normosmia. Multiple regression adjusted by the covariates participants’ age and education level showed a positive association between odour identification and the cognitive inhibition response (SCWT-interference; Beta = 0.29; p = .034). The odour discrimination capacity was not a predictor of the cognitive executive performance. Our results suggest that both hot and cold executive functions seem to be associated with higher-order olfactory functioning in humans. These results robustly support the hypothesis that olfaction and executive measures have a common neural substrate in PFC and OFC, and suggest that olfaction might be a reliable cognitive marker in psychiatric and neurologic disorders. 相似文献
17.
Zaida Agüera Xandra Romero Jon Arcelus Isabel Sánchez Nadine Riesco Susana Jiménez-Murcia Jana González-Gómez Roser Granero Nuria Custal Monica Montserrat-Gil de Bernabé Salomé Tárrega Rosa M. Ba?os Cristina Botella Rafael de la Torre José C. Fernández-García José M. Fernández-Real Gema Frühbeck Javier Gómez-Ambrosi Francisco J. Tinahones Ana B. Crujeiras Felipe F. Casanueva José M. Menchón Fernando Fernández-Aranda 《PloS one》2015,10(11)
The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome. 相似文献
18.
Highlights? AtBMI1A/B proteins prevent misexpression of embryonic traits in somatic cells ? PRC2 and AtBMI1A/B proteins maintain cells in their differentiated state ? AtBMI1A/B proteins mediate H2A monoubiquitination 相似文献
19.
Rodríguez-Muñoz M de la Torre-Madrid E Gaitán G Sánchez-Blázquez P Garzón J 《Cellular signalling》2007,19(12):2558-2571
Opioid agonists display different capacities to stimulate mu-opioid receptor (MOR) endocytosis, which is related to their ability to provoke the phosphorylation of specific cytosolic residues in the MORs. Generally, opioids that efficiently promote MOR endocytosis and recycling produce little tolerance, as is the case for [d-Ala2, N-MePhe4,Gly-ol5] encephalin (DAMGO). However, morphine produces rapid and profound antinociceptive desensitization in the adult mouse brain associated with little MOR internalization. The regulator of G-protein signaling, the RGS14 protein, associates with MORs in periaqueductal gray matter (PAG) neurons, and when RGS14 is silenced morphine increased the serine 375 phosphorylation in the C terminus of the MOR, a GRK substrate. Subsequently, these receptors were internalized and recycled back to the membrane where they accumulated on cessation of antinociception. These mice now exhibited a resensitized response to morphine and little tolerance developed. Thus, in morphine-activated MORs the RGS14 prevents GRKs from phosphorylating those residues required for β-arresting-mediated endocytosis. Moreover morphine but not DAMGO triggered a process involving calcium/calmodulin-dependent kinase II (CaMKII) in naïve mice, which contributes to MOR desensitization in the plasma membrane. In RGS14 knockdown mice morphine failed to activate this kinase. It therefore appears that phosphorylation and internalization of MORs disrupts the CaMKII-mediated negative regulation of these opioid receptors. 相似文献
20.
Catalán V Gómez-Ambrosi J Rodríguez A Ramírez B Silva C Rotellar F Hernández-Lizoain JL Baixauli J Valentí V Pardo F Salvador J Frühbeck G 《The Journal of nutritional biochemistry》2011,22(7):634-641