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11.
Regine Willumeit Sérgio S. Funari Beatriz Pozo Navas Sebastian Linser 《生物化学与生物物理学报:生物膜》2005,1669(2):125-134
We have developed a novel α-helical peptide antibiotic termed NK-2. It efficiently kills bacteria, but not human cells, by membrane destruction. This selectivity could be attributed to the different membrane lipid compositions of the target cells. To understand the mechanisms of selectivity and membrane destruction, we investigated the influence of NK-2 on the supramolecular aggregate structure, the phase transition behavior, the acyl chain fluidity, and the surface charges of phospholipids representative for the bacterial and the human cell cytoplasmic membranes. The cationic NK-2 binds to anionic phosphatidylglycerol liposomes, causing a thinning of the membrane and an increase in the phase transition temperature. However, this interaction is not solely of electrostatic but also of hydrophobic nature, indicated by an overcompensation of the Zeta potential. Whereas NK-2 has no effect on phosphatidylcholine liposomes, it enhances the fluidity of phosphatidylethanolamine acyl chains and lowers the phase transition enthalpy of the gel to liquid cristalline transition. The most dramatic effect, however, was observed for the lamellar/inverted hexagonal transition of phosphatidylethanolamine which was reduced by more than 10 °C. Thus, NK-2 promotes a negative membrane curvature which can lead to the collapse of the phosphatidylethanolamine-rich bacterial cytoplasmic membrane. 相似文献
12.
de Navas LF Reed H Akam M Barrio R Alonso CR Sánchez-Herrero E 《Development (Cambridge, England)》2011,138(1):107-116
Although most metazoan genes undergo alternative splicing, the functional relevance of the majority of alternative splicing products is still unknown. Here we explore this problem in the Drosophila Hox gene Ultrabithorax (Ubx). Ubx produces a family of six protein isoforms through alternative splicing. To investigate the functional specificity of the Ubx isoforms, we studied their role during the formation of the Drosophila halteres, small dorsal appendages that are essential for normal flight. Our work shows that isoform Ia, which is encoded by all Ubx exons, is more efficient than isoform IVa, which lacks the amino acids coded by two small exons, in controlling haltere development and regulating Ubx downstream targets. However, our experiments also demonstrate that the functional differences among the Ubx isoforms can be compensated for by increasing the expression levels of the less efficient form. The analysis of the DNA-binding profiles of Ubx isoforms to a natural Ubx target, spalt, shows no major differences in isoform DNA-binding activities, suggesting that alternative splicing might primarily affect the regulatory capacity of the isoforms rather than their DNA-binding patterns. Our results suggest that to obtain distinct functional outputs during normal development genes must integrate the generation of qualitative differences by alternative splicing to quantitative processes affecting isoform protein expression levels. 相似文献
13.
Fernández-Cruz ML Valdehita A Alonso M Mann E Herradón B Navas JM 《Life sciences》2011,88(17-18):774-783
AimsPifithrin α (PFTα), an inhibitor of the p53 protein, is regarded as a lead compound for cancer and neurodegenerative disease therapy. There is some evidence that this compound activates the aryl hydrocarbon receptor (AhR) in a complete independent way of the p53 inhibition and that it is easily converted to its condensation product pifithrin β (PFTβ). The aim of this study was to explore the ability of PFTα and of PFTβ to induce a variety of AhR mediated processes.Main methodsComputational analysis using quantum chemical calculations and chemical analysis have been used to study the conformation of the compounds as well as the cyclization reaction. The AhR mediated processes of these compounds have been studied in a rainbow trout cell line (RTG-2) and in a rat hepatoma cell line (H4IIE).Key findingsPFTα molecule could not take a planar conformation required for AhR activation whereas PFTβ showed a conformation similar to those of the prototypical AhR ligand β-naphthoflavone. In both cell lines, PFTα and PFTβ provoked different responses related with AhR activation. However, when cyclization of PFTα to PFTβ was hampered by acetylation of the exocyclic nitrogen, all these responses were not observed. These results lead to the conclusion that the activation of the AhR is probably caused by PFTβ instead of PFTα.SignificanceSince PFTα is a promising compound for the development of new pharmaceuticals inhibiting p53, the chemical instability of this compound as well as the capacity of its transformation product should be taken into account. 相似文献
14.
Barbara Tllez‐Robledo Concepcion Manzano Angela Saez Sara Navarro‐Neila Javier Silva‐Navas Laura de Lorenzo Mary‐Paz Gonzlez‐García Ren Toribio Arthur G. Hunt Roberto Baigorri Ilda Casimiro Siobhan M. Brady M. Mar Castellano J. Carlos del Pozo 《The Plant journal : for cell and molecular biology》2019,99(6):1203-1219
15.
Luz-María Torres Liliana Rivera-Espinosa Juan L. Chávez-Pacheco Carlos F. Navas Joel A. Demetrio Radamés Alemón-Medina Francisca Trujillo Martín Pérez Martha M. Zapata Rocío Cárdenas Citlaltepetl Salinas Arnoldo Aquino Rafael Velázquez-Cruz Manuel-de-Jesús Castillejos 《PloS one》2015,10(11)
Ifosfamide blood concentrations are necessary to monitor its therapeutic response, avoiding any adverse effect. We developed and validated an analytical method by UPLC-MS/MS to quantify ifosfamide in dried blood spots (DBS). Blood samples were collected on Whatman 903® filter paper cards. Five 3 mm disks were punched out from each dried blood spot. Acetonitrile and ethyl acetate were used for drug extraction. Chromatographic separation was carried out in an Acquity UPLC equipment with a BEH-C18 column, 2.1 x 100 mm, 1.7 μm (Waters®). The mobile phase consisted in 5 mM ammonium formate and methanol:acetonitrile (40:48:12 v/v/v) at 0.2 mL/min. LC-MS/MS detection was done by ESI+ and multiple reaction mode monitoring, ionic transitions were m/z1+ 260.99 > 91.63 for ifosfamide and 261.00 > 139.90 for cyclophosphamide (internal standard). This method was linear within a 100–10000 ng/mL range and it was accurate, precise and selective. Ifosfamide samples in DBS were stable for up to 52 days at -80°C. The procedure was tested in 14 patients, ages 1 month to 17 years (9 males and 5 females), with embryonic tumours treated with ifosfamide, alone or combined, at a public tertiary referral hospital. Ifosfamide blood levels ranged from 11.1 to 39.7 μmol/L at 12 hours after the last infusion, while 24-hour levels ranged from 0.7–19.7 μmol/L. The median at 12 hours was 19.5 μmol/L (Q25 14.4–Q75 29.0) and 3.8 μmol/L (Q25 1.5–Q75 9.9) at 24 hours, p<0.001. This method is feasible to determine ifosfamide plasma levels in paediatric patients. 相似文献
16.
Bishop MJ Berman J Bigham EC Garrison DT Gobel MJ Hodson SJ Irving PE Liacos JA Minick DJ Navas F Saussy DL Speake JD 《Bioorganic & medicinal chemistry letters》2001,11(21):2871-2874
2-(Anilinomethyl)imidazolines with 2'-esters or 2'-amides are potent agonists of the cloned human alpha(1)-adrenoceptors in vitro. The size and shape of the ortho substituent can have significant effects on the potency, efficacy, and subtype selectivity of these 2-(anilinomethyl)imidazolines. alpha(1A)-subtype selective agonists have been identified. 相似文献
17.
Cellular redox state and activating protein-1 are involved in ascorbate effect on calcitriol-induced differentiation 总被引:1,自引:0,他引:1
G. López-Lluch M. -V. Blázquez R. Pérez-Vicente A. Macho M. I. Burón F. J. Alcaín E. Muñoz P. Navas 《Protoplasma》2001,217(1-3):129-136
Summary Ascorbate has been related to the differentiation of several mesenchymal cells including haematopoietic cells. We have previously demonstrated that ascorbate enhances the activity of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on monocytic differentiation of HL-60 cells. Here, we show that ascorbate-mediated modification of cellular redox state and AP-1 (activating protein-1) DNA binding during early phases are related to the enhancing effect of ascorbate on differentiation. Ascorbate, but not its fully oxidized form, dehydroascorbate, or an ascorbate analogue with a low rate of oxidation, ascorbate-2-phosphate, enhanced the differentiation induced by 1,25(OH)2D3, modified cytosolic reactive oxygen species levels and mitochondrial redox potential (m), and modulated AP-1 DNA binding in HL-60 cells. Ascorbate itself increased AP-1 binding to DNA in noninduced cells, whereas it inhibited AP-1 binding in 1,25(OH)2D3-induced cells. However, ascorbate increased the mRNA levels ofc-jun, junB. andc-fos in 1,25(OH)2D3-induced cells. Taken together, these results suggest that the enhancing effect of ascorbate on HL-60 differentiation induced by 1,25(OH)2D3 is related to its effect on the cellular redox state and the modulation of AP-1 activity.Abbreviations 1,25-(OH)2D3
1,25-dihydroxyvitamin D3
- m
mitochondrial transmembrane potential
- AP-1
activating protein-1
- Asc-2-P
ascorbate-2-phosphate
- DHA
dehydroascorbate
- DiOC6(3)
3,3-dihexyloxacarboxyanine iodide
- EMSA
electromobility shift assay
- NBT
nitroblue tetrazolium
- ROS
reactive oxygen species 相似文献
18.
Bishop MJ Barvian KA Berman J Bigham EC Garrison DT Gobel MJ Hodson SJ Irving PE Liacos JA Navas F Saussy DL Speake JD 《Bioorganic & medicinal chemistry letters》2002,12(3):471-475
Novel 2'-heteroaryl-2-(phenoxymethyl)imidazolines have been identified as potent agonists of the cloned human alpha(1)-adrenoceptors in vitro. The nature of the 2'-heteroaryl group can have significant effects on the potency, efficacy, and subtype selectivity in this series. alpha(1A) Subtype selective agonists have been identified. 相似文献
19.
Navas CA 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》2002,133(3):469-485
A well-defined macroecological pattern is the decline in biodiversity with altitude. However, this decline is taxa-specific. For example, amphibians are more diverse than squamates at extreme elevations in the tropical Andes, but this pattern is reversed at extreme elevations in the southern latitudes. Several ecophysiological and evolutionary factors may be related to this difference. At high-elevations in southern latitudes temperature differs dramatically among seasons and dry soils dominate, characteristics that appear to favor lizard physiological ecology. Tropical high altitudes, in contrast, are humid and offer abundant and diverse water resources. These characteristics allow for a richer anuran community but might complicate lizard egg development through temperature and oxygen constrains. Differences in strategies of thermal adaptation might also modulate diversity patterns. The thermal physiology of anurans is extremely labile so that behavioral and physiological performance is maintained despite an altitudinal decrease in field body temperature. Lizards, in contrast, exhibit a conservative thermal physiology and rely on behavioral thermoregulation to face cold and variable temperatures. Both, lizard behavioral strategies and anuran physiological adjustments seem equally efficient in allowing ecological success and diversification for both groups in the tropics up to approximately 3000 m. At higher elevations physiological thermal adaptation is required, and lizards are ecologically constrained, perhaps at various ontogenetic stages. Patterns of biodiversity along environmental clines can be better understood through a physiological approach, and can help to refine and propose hypotheses in evolutionary physiology. 相似文献
20.
Ceramide-dependent caspase 3 activation is prevented by coenzyme Q from plasma membrane in serum-deprived cells 总被引:4,自引:0,他引:4
Navas P Fernandez-Ayala DM Martin SF Lopez-Lluch G De Caboa R Rodriguez-Aguilera JC Villalba JM 《Free radical research》2002,36(4):369-374
Coenzyme Q (CoQ) is the key factor for the activity of the eukaryotic plasma membrane electron transport chain. Consequently, CoQ is essential in the cellular response against redox changes affecting this membrane. Serum withdrawal induces a mild oxidative stress, which produces lipid peroxidation in membranes. In fact, apoptosis induced by serum withdrawal can be prevented by several antioxidants including CoQ. Also, CoQ can maintain cell growth in serum-limiting conditions, whereas plasma membrane redox system (PMRS) inhibitors such as capsaicin, which compete with CoQ, inhibit cell growth and induce apoptosis. To understand how plasma membrane CoQ prevents oxidative stress-induced apoptosis we have studied the induction of apoptosis by serum withdrawal in CEM cells and its modulation by CoQ. Serum-withdrawal activates neutral sphingomyelinase (N-SMase), ceramide release and caspase-3-related proteases. CoQ addition to serum-free cultures inhibited a 60% N-SMase activation, an 80% ceramide release, and a 50% caspase-3 activity induced by serum deprivation. Caspase activation dependent on ceramide release since C 2 -ceramide was only able to mimic this effect in 10% foetal calf serum cultured cells but not in serum-free cultures. Also, in vitro experiments demonstrated that C 2 -ceramide and ceramide-rich lipid extracts directly activated caspase-3. Taken together, our results indicate that CoQ protects plasma membrane components and controls stress-mediated lipid signals by its participation in the PMRS. 相似文献