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71.
Proprotein processing is essential for HIV infectivity. Cellular trans-Golgi network (TGN) serine proteases (e.g., furin) are required to cleave HIV envelope gp160 to gp120. In addition, HIV protease (PR), an aspartyl protease, cleaves p55(Gag) to p24, etc., in budding virions. alpha1-Antitrypsin (alpha(1)AT) is cleaved by serine proteases, causing a conformational change in alpha(1)AT that sequesters and so inactivates the protease. alpha(1)AT blocks both gp160 and p55 processing, and so is a powerful inhibitor of HIV replication. We hypothesized that alpha(1)AT inhibited gp160 and p55 processing via different mechanisms, and that in both cases, alpha(1)AT bound and was itself cleaved by the proteases whose activities were blocked. alpha(1)AT delivered by SV(AT), a recombinant, Tag-deleted SV40-derived vector, localized to the TGN, co-precipitated with furin, and depleted furin from the TGN. After SV(AT) transduction and HIV challenge, alpha(1)AT was detected in resulting nascent immature HIV-1 virions. alpha(1)AT also blocked incorporation of the enzymatically active dimeric form of PR into HIV virions. Western analysis using recombinant proteins showed that alpha(1)AT directly bound HIV PR, and was cleaved by it. The simultaneous inhibition of two different steps in HIV morphogenesis both increases alpha(1)AT antilentiviral activity and decreases the possibility that HIV mutations will allow escape from inhibition. 相似文献
72.
Marie-Odile Parat Marie-Jeanne Richard Marie Th r se Leccia Pierre Amblard Alain Favier Jean Claude B ani 《Free radical research》1995,23(4):339-351
Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H2O2 cytotoxicity. 相似文献
73.
Vincent Laizé Pierre Ripoche Frédérique Tacnet 《Protein expression and purification》1997,11(3):284-288
The yeastSaccharomyces cerevisiaewas used for heterologous expression of the human CHIP28 water Aquaporin-1 channel (Aquaporin-1). A nine-amino-acid epitope of the influenza hemagglutinin protein (HA epitope), recognized by the monoclonal antibody 12CA5, was chosen to tag CHIP28 at its N-terminus. Epitope-tagged CHIP28 was purified from yeast extracts by immunochromatography on protein A/12CA5-coupled beads, after KI extraction and detergent solubilization, then concentrated by anion exchange chromatography. Purified protein was reconstituted in proteoliposomes and was shown to function as a water channel by stopped-flow spectrophotometry. This study demonstrates that the yeast has the capacity to produce functional aquaporins at levels sufficient for biochemical and biophysical analyses. 相似文献
74.
Electron transport has been studied by flash absorption and EPR spectroscopies at 10–30 K in Photosystem I particles prepared with digitonin under different redox conditions. In the presence of ascorbate, an irreversible charge separation is progressively induced at 10 K between P-700 and iron-sulfur center A by successive laser flashes, up to a maximum which corresponds to about two-thirds of the reaction centers. In these centers, heterogeneity of the rate for center A reduction is also shown. In the other third of reaction centers, the charge separation is reversible and relaxes with a t1/2 ≈ 120 μs. When the iron-sulfur centers A and B are prereduced, the 120 μs relaxation becomes the dominant process (70–80% of the reaction centers), while a slow component (t1/2 = 50–400 ms) reflecting the recombination between P-700+ and center X− occurs in a minority of reaction centers (10–15%). Flash absorption and EPR experiments show that the partner of P-700+ in the 120 μs recombination is neither X nor a chlorophyll but more probably the acceptor A−1 as defined by Bonnerjea and Evans (Bonnerjea, J. and Evans, M.C.W. (1982) FEBS Lett. 148, 313–316). The role of center X in low-temperature electron flow is also discussed. 相似文献
75.
Ulrich Membe Femoe Hermine Boukeng Jatsa Valentin Greigert Julie Brunet Catherine Cannet Mrim Christian Kenfack Nestor Gipwe Feussom Joseph Bertin Kadji Fassi Emilenne Tienga Nkondo Ahmed Abou-Bacar Alexander Wilhelm Pfaff Thophile Dimo Pierre Kamtchouing Louis-Albert Tchuem Tchuent 《PLoS neglected tropical diseases》2022,16(4)
BackgroundOne of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice.Methodology/Principal findingsTwo months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-β gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2.Conclusion/SignificanceThis study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model. 相似文献
76.
77.
Tony Robinet Eric Feunteun Philippe Keith Gérard Marquet Jean-Michel Olivier Elodie Réveillac Pierre Valade 《Environmental Biology of Fishes》2007,78(2):93-105
Anguillid eels were sampled from permanent rivers in the Réunion and Mauritius islands, western Indian Ocean, with a standardized
electrofishing method. A. marmorata was very dominant, corresponding to 91.7 and 90.7% of all the eels collected in Réunion and Mauritius, respectively. Three
other species (A. mossambica, A. bicolor bicolor and A. nebulosa labiata) were also present in both islands. A. marmorata showed a strong altitudinal gradient of densities from the lower to upper zones, especially in the younger stages (TL <250 mm),
while A. mossambica was only found in the upper zones and A. bicolor bicolor occurred only in the lower zones (A. nebulosa labiata was rare). The eel species composition in freshwaters of both islands is very similar because these two adjoining islands
are located in the same trail of drifting marine larvae. Mean estimated eel biomasses were noticeably low (11.1 and 22.2 kg ha−1 in Réunion and Mauritius islands, respectively), especially when compared to those of other tropical insular systems without
any eel fishery (Comoros or Polynesia, more than 100 kg ha−1). Nevertheless, the fluvial recruitment of A. marmorata seemed to be regular during the surveyed period, staggering from October to April. The obvious lack of large eels in Mauritius
but more significantly in Réunion suggests a high pressure from traditional fishery, and the local reproductive turnover is
uncertain. Because sexual maturation seems to occur at a large body size for A. marmorata, as for temperate species, the Réunion and Mauritius rivers may only have a weak contribution to the regional production
of spawners. However, the giant mottled eel population in the western Indian Ocean is believed to be panmictic at the regional
scale, and may not rely exclusively on these islands’ contribution. A comparison is made with those of freshwater systems
in other tropical islands. 相似文献
78.
Matrix metalloproteinases (MMPs) are essential contributors to a microenvironment that promotes tumour progression. During the two last decades, inhibition of MMPs has become the focus of considerable interest for cancer therapy, and numerous synthetic metalloproteinase inhibitors have been developed by the pharmaceutical industry. However, clinical trials have shown disappointing efficacy or unexpected toxicity and new targets are thus eagerly awaited. The identification of endocytic clearance of several MMPs by the low-density lipoprotein receptor-related protein (LRP) might provide insight into novel strategies for controlling MMP level during malignant processes. This review attempts to summarize recent aspects on the cellular and molecular basis of LRP-mediated endocytic disposal of MMPs. 相似文献
79.
Vandrea Carla De Souza Muriel Rabilloud Pierre Cochat Luciano Selistre Aoumeur Hadj-Aissa Behrouz Kassai Bruno Ranchin Ulla Berg Maria Herthelius Laurence Dubourg 《PloS one》2012,7(12)
Background/Objective
Plasma-creatinine-based equations to estimate the glomerular filtration rate are recommended by several clinical guidelines. In 2009, Schwartz et al. adapted the traditional Schwartz equation to children and adolescents but did not find different k-coefficients between children and adolescents (k = 36.5 for all patients). We reevaluated the coefficient of the 2009-Schwartz formula according to sex and age in a pediatric population.Patients/Methods
We used linear mixed-effects models to reestimate the 2009-Schwartz k-coefficient in 360 consecutive French subjects aged 1 to 18 years referred to a single centre between July 2003 and July 2010 (965 measurements). We assessed the agreement between the estimated glomerular filtration rate obtained with the new formula (called Schwartz-Lyon) and the rate measured by inulin clearance. We then compared this agreement to the one between the measured glomerular filtration rate and 2009-Schwartz formula, first in the French then in a Swedish cohort.Results
In Schwartz-Lyon formula, k was estimated at 32.5 in boys <13 years and all girls and at 36.5 in boys aged ≥13 years. The performance of this formula was higher than that of 2009-Schwartz formula in children <13 years. This was first supported by a statistically significant reduction of the overestimation of the measured glomerular filtration rate in both cohorts, by better 10% and 30% accuracies, and by a better concordance correlation coefficient.Conclusions
The performance and simplicity of Schwartz formula are strong arguments for its routine use in children and adolescents. The specific coefficient for children aged <13 years further improves this performance. 相似文献80.