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1.
Ernst Wm. Spannhake Terry L. Adams Steven R. Kleeberger 《Prostaglandins & other lipid mediators》1985,30(6):1041-1055
The effects of repeated antigen exposure on the synthesis of mediators by lung tissues are not well understood. To investigate the influence of antigen challenge on the synthesis of prostaglandins by central airway and peripheral lung tissues, fourteen sensitive sheep underwent biweekly exposure to aerosolized antigen (7) or saline (7). Following the fifth exposure, microsomal and high speed supernatant fractions were prepared from trachealis muscle and lung parenchyma. Synthesis of thromboxane (TX) A2, prostaglandin (PG) D2 and PGI2 from the PG endoperoxide intermediate, PGH2, was assayed over a range of substrate concentrations from 3–200 uM. Synthesis of PGI2 by trachealis microsomes was approximately 5-fold greater than that of TXA2. PGI2 and TXA2 production was identical in tracheal preparations from Ascaris- and saline-exposed animals. In parenchymal tissues, where TXA2 production predominated over PGI2 by 9-fold, preparations from Ascaris- exposed animals synthesized 50% more TXA2 than controls at PGH2 concentrations of 25 uM and above, whereas synthesis of PGI2 and PGD2 were similar in preparations from both groups of animals. The density of pulmonary mast cells was decreased by 21% in the Ascaris group, whereas polymorphonuclear leukocyte density was unchanged. These results demonstrate the differential synthesis of TXA2 and PGI2 in central airways and peripheral lung regions of the sheep. They further indicate that repeated exposure of the airways to antigen selectively enhances TXA2 synthesis in the lung periphery of sensitized animals. The site of this increased enzymatic activity, whether in resident cells or newly-infiltrated cells, has not been determined. 相似文献
2.
Alba Minelli Carmela Conte Silvia Grottelli Ilaria Bellezza Carla Emiliani† Juan P. Bolaños‡ 《Journal of neurochemistry》2009,111(4):956-966
Paraquat (1,1'-dimethyl-4,4'-bipyridinium), a widely used non-selective herbicide, is a redox cycling agent with adverse effects on dopamine systems. Epidemiological data have shown that exposure to paraquat is one of the several risk factors for Parkinson's disease. We have already shown that cyclo(His-Pro), an endogenous cyclic dipeptide produced by the cleavage of the thyrotropin releasing hormone, has a cytoprotective effect through a mechanism involving Nrf2 activation that decreases production of reactive oxygen species and increases glutathione synthesis. Using primary neuronal cultures and PC12 cells as targets of paraquat neurotoxicity, we addressed whether and how cyclo(His-Pro) causes cellular protective response against paraquat-mediated cell death. We found that cyclo(His-Pro) attenuated reactive oxygen species production, and prevented glutathione depletion by up-regulating Nrf2 gene expression, triggering its nuclear accumulation and activating the expression of heme oxygenase1. These protective effects were abolished by RNA interference-mediated Nrf2 knock down whereas were unaffected by RNA interference-mediated Keap1 knock down. Inhibition of heme oxygenase activity decreased cyclo(His-Pro)-induced neuroprotection. These results suggest that cyclo(His-Pro), acting as a selective activator of the brain modulable Nrf2 pathway, may be a promising candidate as neuroprotective agent that act through induction of phase II genes. 相似文献
3.
Marta Tejera-Alhambra Armanda Casrouge Clara de Andrés Ansgar Seyfferth Rocío Ramos-Medina Bárbara Alonso Janet Vega Lidia Fernández-Paredes Matthew L. Albert Silvia Sánchez-Ramón 《PloS one》2015,10(6)
Multiple sclerosis, the most common cause of neurological disability in young population after trauma, represents a significant public health burden. Current challenges associated with management of multiple sclerosis (MS) patients stem from the lack of biomarkers that might enable stratification of the different clinical forms of MS and thus prompt treatment for those patients with progressive MS, for whom there is currently no therapy available. In the present work we analyzed a set of thirty different plasma cytokines, chemokines and growth factors present in circulation of 129 MS patients with different clinical forms (relapsing remitting, secondary progressive and primary progressive MS) and 53 healthy controls, across two independent cohorts. The set of plasma analytes was quantified with Luminex xMAP technology and their predictive power regarding clinical outcome was evaluated both individually using ROC curves and in combination using logistic regression analysis. Our results from two independent cohorts of MS patients demonstrate that the divergent clinical and histology-based MS forms are associated with distinct profiles of circulating plasma protein biomarkers, with distinct signatures being composed of chemokines and growth/angiogenic factors. With this work, we propose that an evaluation of a set of 4 circulating biomarkers (HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4) in MS patients might serve as an effective tool in the diagnosis and more personalized therapeutic targeting of MS patients. 相似文献
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Sonia Coni Silvia Maria Serrao Zuleyha Nihan Yurtsever Laura Di Magno Rosa Bordone Camilla Bertani Valerio Licursi Zaira Ianniello Paola Infante Marta Moretti Marialaura Petroni Francesca Guerrieri Alessandro Fatica Alberto Macone Enrico De Smaele Lucia Di Marcotullio Giuseppe Giannini Marella Maroder Enzo Agostinelli Gianluca Canettieri 《Cell death & disease》2020,11(12)
7.
Liane Wehder Günther Ernst Anna C. Crecelius Orlando Guntinas-Lichius Christian Melle Ulrich S. Schubert Ferdinand von Eggeling 《The journal of histochemistry and cytochemistry》2010,58(10):929-937
Carcinoma tissue consists of not only tumor cells but also fibroblasts, endothelial cells or vascular structures, and inflammatory cells forming the supportive tumor stroma. Therefore, the spatial distribution of proteins that promote growth and proliferation in these complex functional units is of high interest. Matrix-assisted laser desorption/ionization imaging mass spectrometry is a newly developed technique that generates spatially resolved profiles of protein signals directly from thin tissue sections. Surface-enhanced laser desorption/ionization mass spectrometry (MS)combined with tissue microdissection allows analysis of defined parts of the tissue with a higher sensitivity and a broader mass range. Nevertheless, both MS-based techniques have a limited spatial resolution. IHC is a technique that allows a resolution down to the subcellular level. However, the detection and measurement of a specific protein expression level is possible only by semiquantitative methods. Moreover, prior knowledge about the identity of the proteins of interest is necessary. In this study, we combined all three techniques to gain highest spatial resolution, sensitivity, and quantitative information. We used frozen tissue from head and neck tumors and chose two exemplary proteins (HNP1–3 and S100A8) to highlight the advantages and disadvantages of each technique. It could be shown that the combination of these three techniques results in congruent but also synergetic data. (J Histochem Cytochem 58:929–937, 2010) 相似文献
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9.
David Dávila Silvia Fernández Ignacio Torres-Alemán 《The Journal of biological chemistry》2016,291(5):2510-2523
Disruption of insulin-like growth factor I (IGF-I) signaling is a key step in the development of cancer or neurodegeneration. For example, interference of the prosurvival IGF-I/AKT/FOXO3 pathway by redox activation of the stress kinases p38 and JNK is instrumental in neuronal death by oxidative stress. However, in astrocytes, IGF-I retains its protective action against oxidative stress. The molecular mechanisms underlying this cell-specific protection remain obscure but may be relevant to unveil new ways to combat IGF-I/insulin resistance. Here, we describe that, in astrocytes exposed to oxidative stress by hydrogen peroxide (H2O2), p38 activation did not inhibit AKT (protein kinase B) activation by IGF-I, which is in contrast to our previous observations in neurons. Rather, stimulation of AKT by IGF-I was significantly higher and more sustained in astrocytes than in neurons either under normal or oxidative conditions. This may be explained by phosphorylation of the phosphatase PTEN at the plasma membrane in response to IGF-I, inducing its cytosolic translocation and preserving in this way AKT activity. Stimulation of AKT by IGF-I, mimicked also by a constitutively active AKT mutant, reduced oxidative stress levels and cell death in H2O2-exposed astrocytes, boosting their neuroprotective action in co-cultured neurons. These results indicate that armoring of AKT activation by IGF-I is crucial to preserve its cytoprotective effect in astrocytes and may form part of the brain defense mechanism against oxidative stress injury. 相似文献
10.
N. A. Volkova N. A. Zinovieva L. A. Volkova L. K. Ernst 《Russian Journal of Genetics》2006,42(1):72-75
The data on the in vitro and in vivo (into embryonic disk) retroviral-mediated transfer of genetic information into chicken embryonic cells are presented. The estimated transformation frequency of the cultured target cells constituted 8 × 10?4 to 5 × 10?3. A transgenic rooster, carrying recombinant DNA in blood, heart, liver, and intestine cells, was obtained. 相似文献