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941.
Tardy AL Giraudet C Rousset P Rigaudière JP Laillet B Chalancon S Salles J Loreau O Chardigny JM Morio B 《Journal of lipid research》2008,49(7):1445-1455
Epidemiological studies suggest that chronic consumption of trans MUFA may alter muscle insulin sensitivity. The major sources of dietary trans MUFA (dairy fat vs. industrially hydrogenated oils) have different isomeric profiles and thus probably different metabolic consequences. These effects may involve alterations in muscle mitochondrial oxidative capacity, which may in turn promote insulin resistance if fatty acid oxidation is reduced. We report that in Wistar rats, an 8 week diet enriched (4% of energy intake) in either dairy, industrial, or control MUFA did not alter insulin and glucose responses to an intraperitoneal glucose tolerance test (1g/kg). In C2C12 myotubes, vaccenic and elaidic acids did not modify insulin sensitivity compared with oleic acid. Furthermore, the ex vivo total, mitochondrial and peroxisomal oxidation rates of [1-(14)C]oleic, vaccenic, and elaidic acids were similar in soleus and tibialis anterior rat muscle. Finally, an 8 week diet enriched in either dairy or industrial trans MUFA did not alter mitochondrial oxidative capacity in these two muscles compared with control MUFA but did induce a specific reduction in soleus mitochondrial ATP and superoxide anion production (P<0.01 vs. control). In conclusion, dietary trans MUFA of dairy or industrial origin have similar effects and do not impair muscle mitochondrial capacity and insulin sensitivity. 相似文献
942.
Morteau O Gerard C Lu B Ghiran S Rits M Fujiwara Y Law Y Distelhorst K Nielsen EM Hill ED Kwan R Lazarus NH Butcher EC Wilson E 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(9):6309-6315
The differential expression of chemokines and chemokine receptors, by tissues and leukocytes, respectively, contributes to the specific accumulation of leukocyte subsets to different tissues. CCR10/CCL28 interactions are thought to contribute to the accumulation of IgA Ab-secreting cells (ASC) to mucosal surfaces, such as the gastrointestinal tract and the lactating mammary gland. Although the role of CCL28 in lymphocyte homing is well established, direct in vivo evidence for CCR10 involvement in this process has not been previously shown. In this study, we describe the generation of a CCR10-deficient mouse model. Using this model, we demonstrate that CCR10 is critical for efficient localization and accumulation of IgA ASC to the lactating mammary gland. Surprisingly, IgA ASC accumulation to the gastrointestinal tract is minimally impacted in CCR10-deficient mice. These results provide the first direct evidence of CCR10 involvement in lymphocyte homing and accumulation in vivo, and demonstrate that reliance on CCR10-mediated recruitment of IgA ASC varies dramatically within mucosal tissues. 相似文献
943.
Human striated muscle samples, from male control and Duchenne muscular dystrophy-affected children, were subjected to cluster-time-of-flight secondary ion mass spectrometry (cluster-ToF-SIMS) imaging using a 25 keV Bi(3)(+) liquid metal ion gun under static SIMS conditions. Spectra and ion density maps, or secondary ion images, were acquired in both positive and negative ion mode over several areas of 500 x 500 microm(2) (image resolution, 256 x 256 pixels). Characteristic distributions of various lipids were observed. Vitamin E and phosphatidylinositols were found to concentrate within the cells, whereas intact phosphocholines accumulated over the most damaged areas of the dystrophic muscles, together with cholesterol and sphingomyelin species. Fatty acyl chain composition varied depending on the region, allowing estimation of the local damage extent. 相似文献
944.
945.
Bergemann M Lespinet O M'Barek SB Daboussi MJ Dufresne M 《Journal of molecular evolution》2008,67(6):631-642
We have performed a genome-wide analysis of the mimp family of miniature inverted-repeat transposable elements, taking advantage of the recent release of the F. oxysporum genome sequence. Using different approaches, we detected 103 mimp elements, corresponding to 75 nonredundant copies, half of which are located on a single small chromosome. Phylogenetic analysis
identified at least six subfamilies, all remarkably homogeneous in size and sequence. Based on high sequence identity in the
terminal inverted repeats (TIRs), mimp elements were connected to different impala members. To gain insights into the mechanisms at the origin and amplification of mimps, we studied the potential of impala to cross-mobilize different mimps, native but also created de novo by inserting a short DNA segment between two TIRs. Our results show that TIR sequences are
the main requirement for mobilization but that additional parameters in the internal region are likely to influence transposition
efficiency. Finally, we show that integration site preference of native versus newly transposed mimps greatly varies in the host genomes used in this study.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Nucleotide sequences of novel mimp3 and mimp4 elements are available under GenBank accession numbers EU833100 and EU833101, respectively. Coordinates of mimp5, mimp6 and of non-classified mimp copies are indicated in Supplementary Table 1. 相似文献
946.
Imola Wilhelm Péter Nagyőszi Attila E. Farkas Pierre‐Olivier Couraud Ignacio A. Romero Babette Weksler Csilla Fazakas Ngo Thi Khue Dung Sándor Bottka Hannelore Bauer Hans‐Christian Bauer István A. Krizbai 《Journal of neurochemistry》2008,107(1):116-126
Because of the relative impermeability of the blood‐brain barrier (BBB), many drugs are unable to reach the CNS in therapeutically relevant concentration. One method to deliver drugs to the CNS is the osmotic opening of the BBB using mannitol. Hyperosmotic mannitol induces a strong phosphorylation on tyrosine residues in a broad spectrum of proteins in cerebral endothelial cells, the principal components of the BBB. Previously, we have shown that among targets of tyrosine phosphorylation are β‐catenin, extracellular signal‐regulated kinase 1/2 and the non‐receptor tyrosine kinase Src. The aim of this study was to identify new signalling pathways activated by hypertonicity in cerebral endothelial cells. Using an antibody array and immunoprecipitation we identified the receptor tyrosine kinase Axl to become tyrosine phosphorylated in response to hyperosmotic mannitol. Besides activation, Axl was also cleaved in response to osmotic stress. Degradation of Axl proved to be metalloproteinase‐ and proteasome‐dependent and resulted in 50–55 kDa C‐terminal products which remained phosphorylated even after degradation. Specific knockdown of Axl increased the rate of apoptosis in hyperosmotic mannitol‐treated cells; therefore, we assume that activation of Axl may be a protective mechanism against hypertonicity‐induced apoptosis. Our results identify Axl as an important element of osmotic stress‐induced signalling. 相似文献
947.
Nav1.4 deregulation in dystrophic skeletal muscle leads to Na+ overload and enhanced cell death
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Hirn C Shapovalov G Petermann O Roulet E Ruegg UT 《The Journal of general physiology》2008,132(2):199-208
Duchenne muscular dystrophy (DMD) is a hereditary degenerative disease manifested by the absence of dystrophin, a structural, cytoskeletal protein, leading to muscle degeneration and early death through respiratory and cardiac muscle failure. Whereas the rise of cytosolic Ca(2+) concentrations in muscles of mdx mouse, an animal model of DMD, has been extensively documented, little is known about the mechanisms causing alterations in Na(+) concentrations. Here we show that the skeletal muscle isoform of the voltage-gated sodium channel, Na(v)1.4, which represents over 90% of voltage-gated sodium channels in muscle, plays an important role in development of abnormally high Na(+) concentrations found in muscle from mdx mice. The absence of dystrophin modifies the expression level and gating properties of Na(v)1.4, leading to an increased Na(+) concentration under the sarcolemma. Moreover, the distribution of Na(v)1.4 is altered in mdx muscle while maintaining the colocalization with one of the dystrophin-associated proteins, syntrophin alpha-1, thus suggesting that syntrophin is an important linker between dystrophin and Na(v)1.4. Additionally, we show that these modifications of Na(v)1.4 gating properties and increased Na(+) concentrations are strongly correlated with increased cell death in mdx fibers and that both cell death and Na(+) overload can be reversed by 3 nM tetrodotoxin, a specific Na(v)1.4 blocker. 相似文献
948.
Désy O Carignan D Caruso M de Campos-Lima PO 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(4):2348-2355
Isopropanol (IPA) is widely used in household applications and constitutes a leading cause of acute alcohol intoxication second only to ethanol. Although the effects of ethanol on the immune system have been extensively studied, far fewer data are available on IPA. Given the structural similarity between the two molecules, we hypothesized that IPA could as well have immunomodulatory properties. We report here that acute IPA exposure is detrimental to human T lymphocyte and NK cell activity in vitro in concentrations as low as 0.08-0.16% (13-26 mM). IPA treatment did not affect receptor-mediated early signaling but had a reproducible and dose-dependent effect on the nuclear translocation of NFAT and AP-1. Furthermore, we show in a model of acute IPA intoxication that animals became immunosuppressed as judged by their reduced ability to release IL-2 and IFN-gamma in the serum in response to staphylococcal enterotoxin B. This effect was also associated to the down-regulation of TNF-alpha production and was sufficiently strong to rescue susceptible animals from enterotoxin-induced toxic shock. Our results suggest that IPA is potentially immunosuppressive to the adaptive and innate immune system and have broad significance given the exposure of the general population to this ubiquitous chemical. 相似文献
949.
Calbo S Delagrèverie H Arnoult C Authier FJ Tron F Boyer O 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(1):408-417
Skeletal muscles account for more than 30% of the human body, yet mechanisms of immunological tolerance to this tissue remain mainly unexplored. To investigate the mechanisms of tolerance to muscle-specific proteins, we generated transgenic mice expressing the neo-autoantigen OVA exclusively in skeletal muscle (SM-OVA mice). SM-OVA mice were bred with OT-I or OT-II mice that possess a transgenic TCR specific for OVA peptides presented by MHC class I or class II, respectively. Tolerance to OVA did not involve clonal deletion, anergy or an increased regulatory T cell compartment. Rather, CD4+ T cell tolerance resulted from a mechanism of ignorance revealed by their response following OVA immunization. In marked contrast, CD8+ T cells exhibited a loss of OVA-specific cytotoxic activity associated with up-regulation of the immunoregulatory programmed death-1 molecule. Adoptive transfer experiments further showed that OVA expression in skeletal muscle was required to maintain this functional tolerance. These results establish a novel asymmetric model of immunological tolerance to muscle autoantigens involving Ag ignorance for CD4+ T cells, whereas muscle autoantigens recognized by CD8+ T cells results in blockade of their cytotoxic function. These observations may be helpful for understanding the breakage of tolerance in autoimmune muscle diseases. 相似文献
950.
Danger signaling through the inflammasome acts as a master switch between tolerance and sensitization 总被引:1,自引:0,他引:1
Watanabe H Gehrke S Contassot E Roques S Tschopp J Friedmann PS French LE Gaide O 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(9):5826-5832
Efficient priming of adaptive immunity depends on danger signals provided by innate immune pathways. As an example, inflammasome-mediated activation of caspase-1 and IL-1beta is crucial for the development of reactive T cells targeting sensitizers like dinitrofluorobenzene (DNFB). Surprisingly, DNFB and dinitrothiocyanobenzene provide cross-reactive Ags yet drive opposing, sensitizing vs tolerizing, T cell responses. In this study, we show that, in mice, inflammasome-signaling levels can be modulated to turn dinitrothiocyanobenzene into a sensitizer and DNFB into a tolerizer, and that it correlates with the IL-6 and IL-12 secretion levels, affecting Th1, Th17, and regulatory T cell development. Hence, our data provide the first evidence that the inflammasome can define the type of adaptive immune response elicited by an Ag, and hint at new strategies to modulate T cell responses in vivo. 相似文献