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131.
Luiz E. M. Cardoso Peter J. Little Mandy L. Ballinger Christina K. Chan Kathleen R. Braun Susan Potter-Perigo Karin E. Bornfeldt Michael G. Kinsella Thomas N. Wight 《The Journal of biological chemistry》2010,285(10):6987-6995
The synthesis of proteoglycans involves steps that regulate both protein and glycosaminoglycan (GAG) synthesis, but it is unclear whether these two pathways are regulated by the same or different signaling pathways. We therefore investigated signaling pathways involved in platelet-derived growth factor (PDGF)-mediated increases in versican core protein and GAG chain synthesis in arterial smooth muscle cells (ASMCs). PDGF treatment of ASMCs resulted in increased versican core protein synthesis and elongation of GAG chains attached to the versican core protein. The effects of PDGF on versican mRNA were blocked by inhibiting either protein kinase C (PKC) or the ERK pathways, whereas the GAG elongation effect of PDGF was blocked by PKC inhibition but not by ERK inhibition. Interestingly, blocking protein synthesis in the presence of cycloheximide abolished the PDGF effect, but not in the presence of xyloside, indicating that GAG synthesis that results from PKC activation is independent from de novo protein synthesis. PDGF also stimulated an increase in the chondroitin-6-sulfate to chondroitin-4-sulfate ratio of GAG chains on versican, and this effect was blocked by PKC inhibitors. These data show that PKC activation is sufficient to cause GAG chain elongation, but both PKC and ERK activation are required for versican mRNA core protein expression. These results indicate that different signaling pathways control different aspects of PDGF-stimulated versican biosynthesis by ASMCs. These data will be useful in designing strategies to interfere with the synthesis of this proteoglycan in various disease states. 相似文献
132.
Carlos Eduardo Cardoso Fedeli Juliana Sekeres Mussalem Luciana Girotto Gentil Simone Katz 《Experimental parasitology》2010,124(2):153-158
A 500 bp fragment encoding an isoform of cysteine proteinase from Leishmania (Leishmania) amazonensis was subcloned and expressed in the pHis vector, resulting in a recombinant protein of 24 kDa, rLacys24. In Western blots of L. (L.) amazonensis extracts, antibodies directed to rLacys24 recognized a cysteine proteinase isoform of 30 kDa. Analysis by fluorescence-activated cell sorter showed a significantly higher expression of CD8+ lymphocytes in animals immunized with rLacys24 plus CFA, whereas a low expression of CD4+ lymphocytes was observed in these animals. The cytotoxicity of lymphocytes isolated from mice immunized with rLacys24 plus CFA on L. (L.) amazonensis-infected macrophages was significantly higher than that observed in the presence of lymphocytes from control animals. Immunization of BALB/c mice with rLacys24 plus CFA resulted in a low but significant decrease of foot lesions after challenge with L. (L.) amazonensis compared to those exhibited by control mice. 相似文献
133.
In an attempt to elucidate the effects of Sporothrix schenckii infection on the immune response, our laboratory has developed a murine model of disseminated sporotrichosis. Helper T cells
can be further subdivided into Th1 and Th2 phenotypes. The differentiation of two subsets of T lymphocytes is driven by IL-12
and IL-4 cytokines, respectively. Th1 cells produce IFN-γ that activate macrophages and promote cell-mediated immunity. In
addition, we found low levels of iNOS and NO production in the initial (1st and 2nd weeks) and final (9th and 10th weeks)
periods of the infection, in contrast with the period of week 4 to 7 of elevated values. The determination of IFN-γ and IL-12
are in agreement with NO/iNOS detection, showing the presence of cellular immune response throughout the infectious process.
However, the production of IL-4 shows an increase in levels after the 5th and 6th weeks suggesting a participation of Th2
response in this period as well. Regarding these results, the study demonstrated that in experimental sporotrichosis infection
the cellular immune response participated throughout the period analyzed as a nitric oxide dependent mechanism. In contrast,
the presence of Th2 response began in the 5th week, suggesting the participation of humoral immune response in advanced stages
of sporotrichosis. 相似文献
134.
Cardoso LS Oliveira SC Pacífico LG Góes AM Oliveira RR Fonseca CT Carvalho EM Araújo MI 《Memórias do Instituto Oswaldo Cruz》2006,101(Z1):339-343
Asthmatics infected with Schistosoma mansoni have a less severe course of asthma and an inhibition of the Th2 inflammatory response that seems to be mediated by interleukin (IL-10). The objective of this study was to evaluate the capacity of some S. mansoni antigens to stimulate IL-10 production in vitro by cells of asthmatic infected individuals. Peripheral bloods mononuclear cells were stimulated with the S. mansoni recombinant antigens Sm22.6, Sm14, P24, and PIII antigen. IL-10 was measured in the supernatants of cultures. As the recombinant antigens were cloned in Escherichia coli, we blocked contaminant endotoxin with polymyxin B added to the cultures. We demonstrated that all antigens used drove high production of IL-10 in S. mansoni infected individuals (n = 13, 408 +/- 514 and 401 +/- 383 pg/ml, 484 +/- 245 pg/ml, 579 +/- 468 pg/ml, respectively). In asthmatics infected with S. mansoni (n = 21) rP24 induced higher levels of IL-10 (565 +/- 377 pg/ml) when compared to PIII, rSm14 and rSm22.6 (184 +/- 209 pg/ml; 292 +/- 243 pg/ml; 156 +/- 247 pg/ml, respectively). Conclusion: the S. mansoni antigens evaluated in this study stimulated IL-10 production by cells from infected individuals and therefore they have the potential to be used as a modulator of the inflammatory response in asthma. 相似文献
135.
136.
Hugo M. Botelho Sónia S. Leal Isabel Cardoso Kiran Yanamandra Ludmilla A. Morozova-Roche Günter Fritz Cláudio M. Gomes 《The Journal of biological chemistry》2012,287(50):42233-42242
S100A6 is a small EF-hand calcium- and zinc-binding protein involved in the regulation of cell proliferation and cytoskeletal dynamics. It is overexpressed in neurodegenerative disorders and a proposed marker for Amyotrophic Lateral Sclerosis (ALS). Following recent reports of amyloid formation by S100 proteins, we investigated the aggregation properties of S100A6. Computational analysis using aggregation predictors Waltz and Zyggregator revealed increased propensity within S100A6 helices HI and HIV. Subsequent analysis of Thioflavin-T binding kinetics under acidic conditions elicited a very fast process with no lag phase and extensive formation of aggregates and stacked fibrils as observed by electron microscopy. Ca2+ exerted an inhibitory effect on the aggregation kinetics, which could be reverted upon chelation. An FT-IR investigation of the early conformational changes occurring under these conditions showed that Ca2+ promotes anti-parallel β-sheet conformations that repress fibrillation. At pH 7, Ca2+ rendered the fibril formation kinetics slower: time-resolved imaging showed that fibril formation is highly suppressed, with aggregates forming instead. In the absence of metals an extensive network of fibrils is formed. S100A6 oligomers, but not fibrils, were found to be cytotoxic, decreasing cell viability by up to 40%. This effect was not observed when the aggregates were formed in the presence of Ca2+. Interestingly, native S1006 seeds SOD1 aggregation, shortening its nucleation process. This suggests a cross-talk between these two proteins involved in ALS. Overall, these results put forward novel roles for S100 proteins, whose metal-modulated aggregation propensity may be a key aspect in their physiology and function. 相似文献
137.
Gregório Miguel Ferreira de Camargo Diercles Francisco Cardoso Fernanda Maria Monsalves Gil Patrícia Dias da Silva Fonseca Larissa Zetouni Camila Urbano Braz Ana Claudia de Freitas Fábio Ricardo Pablos de Souza Rusbel Raul Aspilcueta-Borquis Fernando Baldi Lucia Galv?o de Albuquerque Luciana Correia de Almeida Regitano Humberto Tonhati 《Molecular biology reports》2012,39(12):10105-10109
Protein JY-1 is a bovine oocyte-specific protein that regulates granulosa cell function and is involved in early embryonic development, influencing the chance of pregnancy. This study investigated molecular markers for the JY-1 gene. Seven SNPs were identified in exon 3 of the gene. The positions of the SNPs in the exon and the respective substitutions are: 163 (T/C), 281 (T/C), 321 (T/C), 532 (T/C), 652 (A/G), 679 (T/C), and 722 (G/C) (GenBank: JN592587 and JF262042.2). SNP 163 is located in a coding region and causes a proline-to-leucine substitution. The other SNPs are located in the 3′UTR region. SNPs 163, 281, 321, and 679 were genotyped in 297 Nellore heifers and the haplotypes were constructed. The haplotypes of JY-1 were not correlated with the traits studied at 5?%. 相似文献
138.
Tatiane Katsue Furuya Patrícia Natália Oliveira da Silva Spencer Luiz Marques Payão Lucas Trevizani Rasmussen Roger Willian de Labio Paulo Henrique Ferreira Bertolucci Ianna Lacerda Sampaio Braga Elizabeth Suchi Chen Gustavo Turecki Naguib Mechawar Jonathan Mill Marília de Arruda Cardoso Smith 《Neurochemistry international》2012
Alzheimer’s Disease (AD) is a neurodegenerative disorder and the most common cause of dementia among the elderly. Efforts have been made to understand the genetic and epigenetic mechanisms involved in the development of this disease. As SORL1 (sortilin-related receptor) and SIRT1 (sirtuin 1) genes have been linked to AD pathogenesis, we aimed to investigate their mRNA expression and promoter DNA methylation in post mortem brain tissues (entorhinal and auditory cortices and hippocampus) from healthy elderly subjects and AD patients. We also evaluated these levels in peripheral blood leukocytes from young, healthy elderly and AD patients, investigating whether there was an effect of age on these profiles. The comparative CT method by Real Time PCR and MALDI-TOF mass spectrometry were used to analyze gene expression and DNA methylation, respectively. SORL1 gene was differently expressed in the peripheral blood leukocytes and might act as a marker of aging in this tissue. Furthermore, we found that SORL1 promoter DNA methylation might act as one of the mechanisms responsible for the differences in expression observed between blood and brain for both healthy elderly and AD patients groups. The impact of these studied genes on AD pathogenesis remains to be better clarified. 相似文献
139.
do Prado MF Coelho AC de Brito JP Ferreira DO Junior AW Menecucci Cda S de Queiroz AB Garcia LB Cardoso CL Tognim MC 《Letters in applied microbiology》2012,54(6):564-567
Aims: The objective of this study was to assess the antimicrobial efficacy of alcohol‐based hand gels according to European Norm 1500 (EN 1500). Methods and Results: We assessed the antimicrobial efficacy of 12 alcohol‐based hand gels produced in Brazil, containing 70% w/w or v/v ethyl alcohol as the active ingredient, according to EN 1500, with a 30‐s application. In addition, 70% w/w ethyl alcohol and three alcohol‐based hand rubs commonly used in Europe and effective according to EN 1500 were also tested. Eight of 12 (67%) alcohol‐based hand gels produced in Brazil failed by EN 1500. In contrast, 70% w/w ethyl alcohol and European alcohol‐based hand rubs were approved by EN 1500. Conclusions: In this study, the majority of Brazilian alcohol‐based hand gels showed limited efficacy on hand hygiene within 30 s. Significance and Impact of the Study: The findings of this study may be used as an important argument to motivate Brazilian manufacturers to improve the antimicrobial efficacy of alcohol‐based hand gels, because it is prudent to suppose that alcohol‐based hand gels can be recommended for use in healthcare settings only if they show antimicrobial activity at least similar to that of alcohol‐based liquid preparations, including the traditional 70% w/w ethyl alcohol. 相似文献
140.
Although many studies have evaluated the possible rules used by males to settle territorial contests, few have simultaneously
considered the possibility of mutual or self-assessment of fighting ability and the effect of prior residence on the chances
of winning. Here, we experimentally investigated the influence of previous residency on the development and outcome of contests
between males of the butterfly Hermeuptychia fallax. By comparing the frequency of resident victories in nonmanipulated disputes versus interactions in which both rivals were
induced to behave as residents, we showed that prior residency may interact with body mass in contest resolution. In nonmanipulated
disputes, resident males showed high winning probabilities, although they were similar to losers in body mass. However, when
both males behaved as residents, the disputes were longer and were settled in favor of the heavier male. This indicates that,
although residency is an important component of male willingness to fight, it is not the only factor influencing conflict
resolution. Despite the correlation between body mass and territorial success, the weight of neither winners nor losers correlated
with fighting duration. We conclude that residence asymmetry may sometimes conceal male traits important to contest resolution
and that it may obscure the identification of the assessment strategy used in contests. 相似文献