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121.
Nativelle-Serpentini C Moslemi S Yous S Park CH Lesieur D Sourdaine P Séralini GE 《Journal of enzyme inhibition and medicinal chemistry》2004,19(2):119-127
New compounds were tested in vitro on aromatase activity in human placental and equine testicular microsomes. Equine aromatase, very well characterized biochemically, is used as a comparative model to understand the mechanism of aromatase inhibition. Among 15 molecules screened, 5 of them (11-15) strongly inhibit human and equine aromatases with IC50 values ranging from 13-85nM and from 23-103nM respectively. These results were corroborated by Ki/Km values. Moreover, spectral studies showed a type II spectrum with both enzymes, which is characteristic of an interaction between the nitrogen atom of the molecule and the heme of the cytochrome P450. Compound 12, which has the lowest IC50 and Ki/Km ratio, inactivates aromatase in a dose and time-dependent manner. This might be very important for the treatment of estrogen-dependent diseases such as breast cancer. Finally, MTT assays on E293 cells revealed that the molecules were not cytotoxic. 相似文献
122.
Yegneswaran S Smirnov MD Safa O Esmon NL Esmon CT Johnson AE 《The Journal of biological chemistry》1999,274(9):5462-5468
The effect of replacing the gamma-carboxyglutamic acid domain of activated protein C (APC) with that of prothrombin on the topography of the membrane-bound enzyme was examined using fluorescence resonance energy transfer. The average distance of closest approach (assuming kappa2 = 2/3) between a fluorescein in the active site of the chimera and octadecylrhodamine at the membrane surface was 89 A, compared with 94 A for wild-type APC. The gamma-carboxyglutamic acid domain substitution therefore lowered and/or reoriented the active site, repositioning it close to the 84 A observed for the APC. protein S complex. Protein S enhances wild-type APC cleavage of factor Va at Arg306, but the inactivation rate of factor Va Leiden by the chimera alone is essentially equal to that by wild-type APC plus protein S. These data suggest that the activities of the chimera and of the APC.protein S complex are equivalent because the active site of the chimeric protein is already positioned near the optimal location above the membrane surface to cleave Arg306. Thus, one mechanism by which protein S regulates APC activity is by relocating its active site to the proper position above the membrane surface to optimize factor Va cleavage. 相似文献
123.
124.
Competitive interaction of cyclosporins with the Vinca alkaloid-binding site of P-glycoprotein in multidrug-resistant cells 总被引:6,自引:0,他引:6
The mechanism of reversal of resistance to Vinca alkaloids by cyclosporins is unclear. We investigated the molecular mechanism of reversal of Vinca alkaloid resistance by cyclosporin A (CsA) and its nonimmunosuppressive analog O-acetyl C9(1) CsA (SDZ 33-243) in multidrug resistant DC-3F/VCRd-5L Chinese hamster cells. CsA at 3 microM increased vincristine (VCR) sensitivity and almost totally reversed VCR resistance. SDZ 33-243 at 1 microM reduced the IC50 for VCR in resistant cells from 62.0 to 0.00062 microM. CsA and SDZ 33-243 at 10 microM increased [3H]vinblastine (VBL) accumulation in DC-3F/VCRd-5L cells by 27- and 22-fold, respectively. At 10 microM, these compounds also increased [3H]VCR accumulation by 3.5- and 4.0-fold, respectively. [3H]VCR uptake by membrane vesicles from DC-3F/VCRd-5L cells showed high and low affinity components with Michaelis-Menten kinetics, and apparent Km values were 0.140 +/- 0.0523 and 24.8 +/- 6.67 microM, respectively. Kinetic analysis of [3H]VCR uptake in membrane vesicles in the presence of 0.2 microM CsA revealed that CsA competitively inhibited the high affinity [3H]VCR uptake with an apparent inhibition constant (Ki) of 0.126 +/- 0.0173 microM. In addition, CsA and SDZ 33-243 inhibited VBL photoaffinity labeling of P-glycoprotein in a dose-dependent manner, with half-maximum inhibition at 0.5 and 0.4 microM, respectively, compared with that of VBL at 0.6 microM. These data confirm that cyclosporins modulate Vinca alkaloid resistance at least partially through interaction with P-glycoprotein. 相似文献
125.
FcRav2, a gene with a ROGDI domain involved in Fusarium head blight and crown rot on durum wheat caused by Fusarium culmorum
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Francesca Spanu Barbara Scherm Irene Camboni Virgilio Balmas Giovanna Pani Safa Oufensou Nicolo’ Macciotta Matias Pasquali Quirico Migheli 《Molecular Plant Pathology》2018,19(3):677-688
Fusarium culmorum is a soil‐borne fungal pathogen which causes foot and root rot and Fusarium head blight on small‐grain cereals, in particular wheat and barley. It causes significant yield and quality losses and results in the contamination of kernels with type B trichothecene mycotoxins. Our knowledge of the pathogenicity factors of this fungus is still limited. A transposon tagging approach based on the mimp1/impala double‐component system has allowed us to select a mutant altered in multiple metabolic and morphological processes, trichothecene production and virulence. The flanking regions of mimp1 were used to seek homologies in the F. culmorum genome, and revealed that mimp1 had reinserted within the last exon of a gene encoding a hypothetical protein of 318 amino acids which contains a ROGDI‐like leucine zipper domain, supposedly playing a protein–protein interaction or regulatory role. By functional complementation and bioinformatic analysis, we characterized the gene as the yeast Rav2 homologue, confirming the high level of divergence in multicellular fungi. Deletion of FcRav2 or its orthologous gene in F. graminearum highlighted its ability to influence a number of functions, including virulence, trichothecene type B biosynthesis, resistance to azoles and resistance to osmotic and oxidative stress. Our results indicate that the FcRav2 protein (and possibly the RAVE complex as a whole) may become a suitable target for new antifungal drug development or the plant‐mediated resistance response in filamentous fungi of agricultural interest. 相似文献
126.
Ardalan Armin Zhiming Chen Yaocheng Jin Kai Zhang Fei Huang Safa Shoaee 《Liver Transplantation》2018,8(7)
Charge extraction rate in solar cells made of blends of electron donating/accepting organic semiconductors is typically slow due to their low charge carrier mobility. This sets a limit on the active layer thickness and has hindered the industrialization of organic solar cells (OSCs). Herein, charge transport and recombination properties of an efficient polymer (NT812):fullerene blend are investigated. This system delivers power conversion efficiency of >9% even when the junction thickness is as large as 800 nm. Experimental results indicate that this material system exhibits exceptionally low bimolecular recombination constant, 800 times smaller than the diffusion‐controlled electron and hole encounter rate. Comparing theoretical results based on a recently introduced modified Shockley model for fill factor, and experiments, clarifies that charge collection is nearly ideal in these solar cells even when the thickness is several hundreds of nanometer. This is the first realization of high‐efficiency Shockley‐type organic solar cells with junction thicknesses suitable for scaling up. 相似文献
127.
Factor VIIa, in complex with tissue factor (TF), is the serine protease responsible for initiating the clotting cascade. This enzyme complex (TF/VIIa) has extremely restricted substrate specificity, recognizing only three previously known macromolecular substrates (serine protease zymogens, factors VII, IX, and X). In this study, we found that TF/VIIa was able to cleave multiple peptide bonds in the coagulation cofactor, factor V. SDS-PAGE analysis and sequencing indicated the factor V was cleaved at Arg679, Arg709, Arg1018, and Arg1192, resulting in a molecule with a truncated heavy chain and an extended light chain. This product (FVTF/VIIa) had essentially unchanged activity in clotting assays when compared to the starting material. TF reconstituted into phosphatidylcholine vesicles was ineffective as a cofactor for the factor VIIa cleavage of factor V. However, incorporation of phosphatidylethanolamine in the vesicles had little effect over the presence of 20% phosphatidylserine. FVTF/VIIa was as sensitive to inactivation by activated protein C (APC) as thrombin activated factor V as measured in clotting assays or by the appearance of the expected heavy chain cleavage products. The FVTF/VIIa could be further cleaved by thrombin to release the normal light chain, albeit at a significantly slower rate than native factor V, to yield a fully functional product. These studies thus reveal an additional substrate for the TF/VIIa complex. They also indicate a new potential regulatory pathway of the coagulation cascade, i.e., the production of a form of factor V that can be destroyed by APC without the requirement for full activation of the cofactor precursor. 相似文献
128.
Donia Bouaziz Safa Charfeddine Rania Jbir Asma Hammami Lotfi Kamoun Radhia Gargouri-Bouzid 《Plant Cell, Tissue and Organ Culture》2017,128(1):197-209
We developed an efficient system for agrobacterial transformation of plum (Prunus domestica L.) leaf explants using the PMI/mannose and GFP selection system. The cultivar ‘Startovaya’ was transformed using Agrobacterium tumefaciens strain CBE21 carrying the vector pNOV35SGFP. Leaf explants were placed onto a nutrient medium containing various concentrations and combinations of mannose and sucrose to develop an efficient selection system. Nine independent transgenic lines of plum plants were obtained on a regeneration medium containing 20 g/L sucrose and 15 g/L mannose. The highest transformation frequency (1.40?%) was produced using a delayed selection strategy. Starting from the 1st days after transformation and ending by regeneration of shoots from the transgenic callus, selection of transgenic cells was monitored by GFP fluorescence that allowed avoiding formation of escapes. Integration of the manA and gfp transgenes was confirmed by PCR and Southern blotting. The described transformation protocol using a positive PMI/mannose system is an alternative selection system for production of transgenic plum plants without genes of antibiotic and herbicide resistance, and the use of leaf explants enables retention of cultivar traits of plum plants. 相似文献
129.
The objective of this study is the evaluation of health risk of heavy metals in soils of urban community gardens of Baghdad City in Iraq. The soil samples were collected from 14 community gardens and analyzed for Cd, Cr, Cu, Ni, Pb and Zn. The non-carcinogenic hazard index (HI) and carcinogenic risk index (RI) were utilized to evaluate human health risk of heavy metals. The health hazard evaluation showed that there is no non-carcinogenic hazard in light of the fact that the HI values were beneath the threshold value (HI < 1). The HI for children and adults has a descending order of Cd < Cr < Cu < Ni < Pb < Zn. The carcinogenic RI values for Cd, Cr and Ni were over the unacceptable threshold value (RI < 1 × 10?4), demonstrating that there is a serious carcinogenic risk for children and adults in the study area. The carcinogenic RI for children and adults has a descending order of Cr < Cd < Ni. These findings give environment administrators and leaders data on whether therapeutic activities are required to decrease exposure. 相似文献
130.
Novi Silvia Hardiany Adrian Prasetya Karman Aisha Safa Putri Calista Budi Gittanaya Anindyanari Daniell Edward Rahardjo Puti Retasya Novira Rania Rifdah Taufiq Shofiyya Imtiyaz Radiana Dhewayani Antarianto 《Reports of Biochemistry & Molecular Biology》2022,11(2):190
Background:Oxidative stress is defined as the condition in which balance between the synthesis and detoxification of reactive oxygen species in cells is disrupted. This research explored the effects of intermittent and prolonged fasting on malondialdehyde (MDA), carbonyl, reduced glutathione (GSH), and specific activity of catalase as biomarkers for oxidative stress in hearts, brains, and kidneys of New Zealand White (NZW) rabbits.Methods:Fifteen NZW rabbits were divided into control, intermittent fasting (IF), and prolonged fasting (PF) groups. The controls were fed ad lib. IF and PF groups were fasted for 16 and 40 hours, respectively, followed by eight hours of non-fasting, for six days and were sacrificed on the 7th day. One hundred mg of heart, brain, and kidney tissues were homogenized in 1 ml of phosphate-buffered saline. MDA, carbonyl, GSH, and catalase were analyzed by spectrophotometry. Data were analyzed using One-way ANOVA and post hoc test.Results:In heart, MDA was significantly greater in the control than in the IF and PF groups. In brain, GSH was greater in the IF than in the PF and control groups. Also, in brain, catalase specific activity was significantly greater in the control than in the IF and PF groups. In kidney, catalase specific activity was significantly less in the PF than in the control group.Conclusion:The effect of fasting on oxidative stress in various organs showed various responses, however fasting reduced oxidative stress based on MDA and GSH levels in the heart and brain, respectively.Key Words: Fasting, Oxidative stress, Vital organs, Rabbit 相似文献