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111.
Pierre Sicard Stéphanie Delemasure Claudia Korandji Anabelle Segueira-Le grand Benjamin Lauzier Jean-Claude Guilland 《Free radical research》2013,47(3):226-236
Among their pleiotropic effects, statins exert antioxidant and anti-inflammatory properties. The aim of this study was to evaluate in normotensive (WKY) and in spontaneously hypertensive rats (SHR) the effect of rosuvastatin (ROSU) treatment on (1) plasma inflammation markers and endogenous NO synthase inhibitor (ADMA) levels, (2) reactive oxygen species (ROS) generated by circulating leukocytes and (3) vascular oxidative stress and tissue inflammation markers. Plasma cytokines were higher in SHR than in WKY, except for IL-4, which was lower in SHR than in WKY. SHR monocytes exhibited higher production of ROS than did WKY monocytes. In the experimental conditions, ROSU did not modify plasma cholesterol levels in SHR but attenuated the increase in systolic blood pressure. In SHR only, ROSU lessened pro-inflammatory cytokines and ADMA levels, increased IL-4 and reduced ROS production in circulating monocytes. These results demonstrate the beneficial effects of ROSU in SHR, independently of any lowering of cholesterol levels. 相似文献
112.
Jeffrey G. Marblestone Samir Butt Devin M. McKelvey David E. Sterner Michael R. Mattern Benjamin Nicholson Michael J. Eddins 《Cell biochemistry and biophysics》2013,67(1):161-167
The ubiquitin pathway regulates diverse functions including protein localization and stability. The complexity of the pathway involving nearly 40 identified E2 conjugating enzymes and over 600 E3 ligases raises the issue of specificity. With the E2s and E3s fitting into a limited number of classes based on bioinformatics, structures, and proven activities, there is not a clear picture as to what would determine which E2/E3 enzyme pair would be functional. There have been many reports of limited E2/E3 activity profiling with a small number of E2s and E3s. We have expanded on this to investigate the activity of ubiquitin E2s covering the majority of the reported classes/families in concert with a number of E3s implicated in a variety of diseases. Using an ELISA-based assay we screened 10 E3 ligases against a panel of 11 E2s to determine which E2/E3 pairs exhibited E3 autoubiquitylation activity. In addition, the ubiquitin chain linkage preference by certain E2/E3 pairs was investigated. Finally, substrate ubiquitylation was assayed for the E3 ligase MuRF1 using various E2/MuRF1 pairs. These studies demonstrate the utility of identifying the correct E2/E3 pair to monitor specific substrate ubiquitylation. 相似文献
113.
Christopher Shipp Benjamin Weide Evelyna Derhovanessian Graham Pawelec 《Cell stress & chaperones》2013,18(2):145-154
Heat shock proteins (hsps) have been studied in numerous cancer types, but a clear view of their clinical relevance in melanoma remains elusive. Therefore, the aim of this study was to investigate the expression of hsps in melanoma with respect to patient clinical parameters. Using Western immunoblotting, hsps 90, 70, 60, 40 and 32 were observed to be widely expressed in metastatic melanomas (n = 31), while immunofluorescence demonstrated that in the majority of samples these hsps, apart from hsp32, were increased in expression in melanoma cells compared with surrounding non-melanoma cells in situ (n = 8). Correlating hsp expression with patient clinical parameters indicated that greater hsp90 (P < 0.02) and hsp40 (P < 0.03) expression correlated with advanced stage (stage III Vs stage IV), while in the case of hsp40, this was additionally associated with reduced patient survival (P < 0.05). In contrast, higher hsp32 expression was associated with improved patient survival (P < 0.007). On the other hand, the expression of the other hsps did not correlate with any obtainable patient clinical parameters. This study provides further evidence for the importance of hsps in melanoma and for their use as therapeutic targets and biomarkers, but larger-scale follow-up studies are required to confirm these results.
Electronic supplementary material
The online version of this article (doi:10.1007/s12192-012-0363-1) contains supplementary material, which is available to authorized users. 相似文献114.
Benjamin Proshek Lindsay A. Crawford Corey S. Davis Sylvie Desjardins Allison E. Henderson Felix A. H. Sperling 《Journal of Insect Conservation》2013,17(1):155-170
Like many species, the Mormon Metalmark butterfly (Apodemia mormo) has been given conservation ranking in Canada based on limited data. This species is widespread across western North America, but has only two populations in Canada: an “endangered” population in the Similkameen valley of British Columbia, and a “threatened” population in Grasslands National Park (GNP) in Saskatchewan. Here we present genetic data from 1498 base pairs of the cytochrome oxidase I gene sequence and six novel microsatellite loci in order to assess (1) whether the two populations are related, (2) the degree to which they are genetically diverse and demographically stable, and (3) what their relationships are to the nearest unranked populations of A. mormo across the Canada-United States border. Our principal conclusion is that the two populations are not closely related genetically. We also found that the British Columbia population is genetically depauperate and, with the exception of the nearest neighboring populations across the border, not recently genetically connected to other populations in the Pacific Northwest. In comparison, the Saskatchewan population is genetically diverse, and gene flow occurs with several other eastern populations. Population structure was not detected within either the British Columbia or the Saskatchewan populations. This research supports the prior conservation rankings of both populations and provides new insight that will help to inform future management decisions for the Canadian populations of this charismatic butterfly. 相似文献
115.
Arjun Dhanoya Tse Wang Eli Keshavarz‐Moore Ariberto Fassati Benjamin M. Chain 《Traffic (Copenhagen, Denmark)》2013,14(2):165-175
Eukaryotic cells have the ability to uptake and transport endogenous and exogenous DNA in their nuclei, however little is known about the specific pathways involved. Here we show that the nuclear transport receptor importin 7 (imp7) supports nuclear import of supercoiled plasmid DNA and human mitochondrial DNA in a Ran and energy‐dependent way. The imp7‐dependent pathway was specifically competed by excess DNA but not by excess of maltose‐binding protein fused with the classical nuclear localizing signal (NLS) or the M9 peptides. Transport of DNA molecules complexed with poly‐l ‐lysine was impaired in intact cells depleted of imp7, and DNA complexes remained localized in the cytoplasm. Poor DNA nuclear import in cells depleted of imp7 directly correlated with lower gene expression levels in these cells compared to controls. Inefficient nuclear import of transfected DNA induced greater upregulation of the interferon pathway, suggesting that rapid DNA nuclear import may prevent uncontrolled activation of the innate immune response. Our results provide evidence that imp7 is a non‐redundant component of an intrinsic pathway in mammalian cells for efficient accumulation of exogenous and endogenous DNA in the nucleus, which may be critical for the exchange of genetic information between mitochondria and nuclear genomes and to control activation of the innate immune response . 相似文献
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117.
Benjamin Tiburzy Martin Szyska Hiroaki Iwata Navina Chrobok Upasana Kulkarni Misa Hirose Ralf J. Ludwig Kathrin Kalies Jürgen Westermann David Wong Rudolf Armin Manz 《PloS one》2013,8(12)
Autoantibodies are believed to be maintained by either the continuous generation of short-lived plasma cells in secondary lymphoid tissues or by long-lived plasma cells localized in bone marrow and spleen. Here, we show in a mouse model for the autoimmune blistering skin disease epidermolysis bullosa acquisita (EBA) that chronic autoantibody production can also be maintained in inflamed lymph nodes, by plasma cells exhibiting intermediate lifetimes. After EBA induction by immunization with a mCOL7c-GST-fusion protein, antigen-specific plasma cells and CD4 T cells were analyzed. Plasma cells were maintained for months in stable numbers in the draining lymph nodes, but not in spleen and bone marrow. In contrast, localization of mCOL7c-GST -specific CD4 T cells was not restricted to lymph nodes, indicating that availability of T cell help does not limit plasma cell localization to this site. BrdU-incorporation studies indicated that pathogenic mCOL7c- and non-pathogenic GST-specific plasma cells resemble intermediates between short-and long-lived plasma cells with half-lives of about 7 weeks. Immunization with mCOL7c-GST also yielded considerable numbers of plasma cells neither specific for mCOL7c- nor GST. These bystander-activated plasma cells exhibited much shorter half-lives and higher population turnover, suggesting that plasma cell lifetimes were only partly determined by the lymph node environment but also by the mode of activation. These results indicate that inflamed lymph nodes can harbor pathogenic plasma cells exhibiting distinct properties and hence may resemble a so far neglected site for chronic autoantibody production. 相似文献
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