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31.
Direct identification of tyrosine 474 as a regulatory phosphorylation site for the Akt protein kinase 总被引:4,自引:0,他引:4
Conus NM Hannan KM Cristiano BE Hemmings BA Pearson RB 《The Journal of biological chemistry》2002,277(41):38021-38028
Understanding the regulation of Akt has been of major interest for elucidating the control of normal cellular physiology as well as malignant transformation. The paradigm for activation of Akt involves phosphatidylinositol 3-kinase-dependent membrane localization followed by activating phosphorylation of Thr-308 and Ser-473. Many of the activating signals for Akt involve the stimulation of receptor and non-receptor tyrosine kinases, and the most potent activator known is the tyrosine phosphatase inhibitor pervanadate, highlighting a possible role for tyrosine phosphorylation in the regulation of the enzyme. In this study we show that activation of Akt by pervanadate or serum is associated with tyrosine phosphorylation of Akt. In addition, in SKOV3 ovarian carcinoma cells that exhibit high basal levels of Akt activity, Akt was tyrosine-phosphorylated in the basal state, and this phosphorylation was further enhanced by both pervanadate and insulin-like growth factor-1. We have used NH(2)-terminal sequencing and phosphate release analysis to directly identify Tyr-474 as the site of tyrosine phosphorylation. Substitution of Tyr-474 with phenylalanine abolished tyrosine phosphorylation of Akt and resulted in up to 55% inhibition of Akt activation, indicating phosphorylation at Tyr-474 is required for full activation of the kinase. Our data identifies a novel regulatory mechanism for this pleiotropic enzyme that may be applicable to the AGC family of protein kinases given the conserved nature of the COOH-terminal hydrophobic motif containing Tyr-474. 相似文献
32.
Mercury (Hg) is a persistent soil pollutant that affects soil microbial activity. We monitored the changes in soil microbial
biomass and activity of enzymes, including alkaline phosphatase, arylsulfatase, fluorescein diacetate (FDA) hydrolytic activity,
and o-diphenol oxidase (o-DPO) in three soils contaminated with different concentrations of Hg. Increasing levels of Hg, from 0.5 to 10 μmol/g of dried
soil, generally depressed microbial activity; however, the effects of Hg on soil microbial activity depended on soil type
and composition, particularly organic matter content. o-DPO was less affected by Hg than the other three enzymes tested. Our results indicate that the analysis of microbial biomass
content and soil-enzyme activities may be used to predict the soil quality contaminated with Hg. 相似文献
33.
Cristiani F. Bortolatto Cristiano R. Jesse Ethel A. Wilhelm Cristina W. Nogueira 《Life sciences》2010,86(9-10):372-376
AimsStudies have shown that the acute administration of venlafaxine elicits an antidepressant-like effect in the mouse forced swim test (FST) by a mechanism dependent on the l-arginine–nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway. Because it has been reported that NO activates different types of potassium (K+) channels in the brain, this study investigated the involvement of K+ channels in the antidepressant-like effect of venlafaxine in the mouse FST.Main methodsMale adult Swiss mice were pretreated with different K+ channel inhibitors or openers 15 min before venlafaxine administration. After 30 min, the open-field test (OFT) and FST were carried out.Key findingsIntracerebroventricular (i.c.v.) pretreatment of mice with subeffective doses of tetraethylammonium (TEA, a non-specific inhibitor of K+ channels, 25 pg/site), glibenclamide (an ATP-sensitive K+ channel inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K+ channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K+ channel inhibitor, 10 pg/site) was able to potentiate the action of a subeffective dose of venlafaxine (2 mg/kg, i.p.). Moreover, the reduction in the immobility time elicited by an effective dose of venlafaxine (8 mg/kg, i.p.) in the FST was prevented by the pretreatment of mice with the K+ channel openers cromakalim (10 µg/site, i.c.v.) and minoxidil (10 µg/site, i.c.v.). The drugs used in this study did not produce any change in locomotor activity.SignificanceThe results demonstrate that the neuromodulatory effects of venlafaxine, via the inhibition of K+ channels, are possibly involved in its anti-immobility activity in the mouse FST. 相似文献
34.
Luca Salvatore De Santo Michele Torella Gianpaolo Romano Ciro Maiello Marianna Buonocore Ciro Bancone Alessandro Della Corte Nicola Galdieri Gianantonio Nappi Cristiano Amarelli 《PloS one》2015,10(5)
MethodsData on 362 consecutive recipients (mean age: 47.8±13.7, 20.2% female, 18.2% diabetics, 22.1% with previous cardiac operations, 27.6% hospitalized, 84.9±29.4 ml/min preoperative glomerular filtration rate) were analyzed using multivariable logistic regression modeling. Target outcomes were determinants of troponin release, early graft failure (EGF), acute kidney injury (AKI) and operative death.ResultsMean cTnI release measured 24 hours after transplant was 10.9±11.6 μg/L. Overall hospital mortality was 10.8%, EGF 10.5%, and AKI was 12.2%. cTnI release>10 μg/L proved an independent predictor of EGF (OR 2.2; 95% CI, 1.06–4.6) and AKI (OR 1.031; 95% CI, 1.001-1.064). EGF, in turn, proved a determinant of hospital mortality. Risk factors for cTnI>10 μg/L release were: status 2B (OR 0.35; 95% CI, 0.18-0.69, protective), duration of the ischemic period (OR 1.006; 95% CI, 1.001-1.011), previous cardiac operation (OR 2.9; 95% CI, 1.67-5.0), and left ventricular hypertrophy (OR 3.3; 95% CI, 1.9-5.6).ConclusionsMyocardial enzyme leakage clearly emerged as an epiphenomenon of more complicated clinical course. The complex interplay between surgical procedure features, graft characteristics and recipient end-organ function highlights cTnI release as a risk marker of graft failure and acute kidney injury. The search for optimal myocardial preservation is still an issue. 相似文献
35.
Fernando Henrique Magalh?es Leonardo Abdala Elias Cristiano Rocha da Silva Felipe Fava de Lima Diana Rezende de Toledo André Fabio Kohn 《PloS one》2015,10(11)
Presynaptic inhibition (PSI) has been shown to modulate several neuronal pathways of functional relevance by selectively gating the connections between sensory inputs and spinal motoneurons, thereby regulating the contribution of the stretch reflex circuitry to the ongoing motor activity. In this study, we investigated whether a differential regulation of Ia afferent inflow by PSI may be associated with the performance of two types of plantarflexion sensoriomotor tasks. The subjects (in a seated position) controlled either: 1) the force level exerted by the foot against a rigid restraint (force task, FT); or 2) the angular position of the ankle when sustaining inertial loads (position task, PT) that required the same level of muscle activation observed in FT. Subjects were instructed to maintain their force/position at target levels set at ~10% of maximum isometric voluntary contraction for FT and 90° for PT, while visual feedback of the corresponding force/position signals were provided. Unconditioned H-reflexes (i.e. control reflexes) and H-reflexes conditioned by electrical pulses applied to the common peroneal nerve with conditioning-to-test intervals of 21 ms and 100 ms (corresponding to D1 and D2 inhibitions, respectively) were evoked in a random fashion. A significant main effect for the type of the motor task (FT vs PT) (p = 0.005, η2
p = 0.603) indicated that PTs were undertaken with lower levels of Ia PSI converging onto the soleus motoneuron pool. Additionally, a significant interaction between the type of inhibition (D1 vs D2) and the type of motor task (FT vs PT) (p = 0.038, η2
p = 0.395) indicated that D1 inhibition was associated with a significant reduction in PSI levels from TF to TP (p = 0.001, η2
p = 0.731), whereas no significant difference between the tasks was observed for D2 inhibition (p = 0.078, η2
p = 0.305). These results suggest that D1 and D2 inhibitions of the soleus H-reflex are differentially modulated during the performance of plantarflexion FT and PT. The reduced level of ongoing PSI during PT suggests that, in comparison to FT, there is a larger reliance on inputs from muscle spindles primary afferents when the neuromuscular system is required to maintain position-controlled plantarflexion contractions. 相似文献
36.
Gustavo Duarte Emiliano N. Calderon Cristiano M. Pereira Laura F. B. Marangoni Henrique F. Santos Raquel S. Peixoto Adalto Bianchini Clovis B. Castro 《Ecology and evolution》2015,5(20):4555-4566
We describe a completely randomizable flow‐through outdoor mesocosm for climate change and ecotoxicology studies that was built with inexpensive materials. The 16 raceway tanks allow up to 6× water renewal per hour, avoiding changes in natural abiotic seawater conditions. We use an open‐source hardware board (Arduino) that was adapted to control heaters and an innovative CO2 injection system. This system reduced seawater pH up to ?0.9 units and increased temperature up to +6°C in three treatments and a control. Treatments can be continuously compared with the control and vary according to diel fluctuations, thus following the diel range observed in the sea. The mesocosm facility also includes an integrated secondary system of 48 aquaria for ecotoxicology studies. We validated the reproducibility and relevance of our experimental system by analyzing the variation of the total DNA of the microbial community extracted from corals in three elevated temperature scenarios during a 40‐day experiment. We also present data from temperature, acidification, and copper contamination trials, which allowed continuous, reliable, and consistent treatment manipulations. 相似文献
37.
Cristiano?L.P. Oliveira Priscila?R. Santos Andrea?M. Monteiro Antonio?M. Figueiredo?Neto 《Biophysical journal》2014,106(12):2595-2605
This work presents a controlled study of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) structural changes due to in vitro oxidation with copper ions. The changes were studied by small-angle x-ray scattering (SAXS) and dynamic light scattering (DLS) techniques in the case of LDL and by SAXS, DLS, and Z-scan (ZS) techniques in the case of HDL. SAXS data were analyzed with a to our knowledge new deconvolution method. This method provides the electron density profile of the samples directly from the intensity scattering of the monomers. Results show that LDL particles oxidized for 18 h show significant structural changes when compared to nonoxidized particles. Changes were observed in the electrical density profile, in size polydispersity, and in the degree of flexibility of the APO-B protein on the particle. HDL optical results obtained with the ZS technique showed a decrease of the amplitude of the nonlinear optical signal as a function of oxidation time. In contrast to LDL results reported in the literature, the HDL ZS signal does not lead to a complete loss of nonlinear optical signal after 18 h of copper oxidation. Also, the SAXS results did not indicate significant structural changes due to oxidation of HDL particles, and DLS results showed that a small number of oligomers formed in the sample oxidized for 18 h. All experimental results for the HDL samples indicate that this lipoprotein is more resistant to the oxidation process than are LDL particles. 相似文献
38.
Airoldi C Zona C Sironi E Colombo L Messa M Aurilia D Gregori M Masserini M Salmona M Nicotra F La Ferla B 《Journal of biotechnology》2010,156(4):317-324
Curcumin derivatives with high chemical stability, improved solubility and carrying a functionalized appendage for the linkage to other entities, have been synthesized in a straightforward manner. All compounds retained Curcumin ability to bind Aβ peptide oligomers without inducing their aggregation. Moreover all Curcumin derivatives were able to stain very efficiently Aβ deposits. 相似文献
39.
Eduardo Vilanova Cristiano Coutinho Guilherme Maia Paulo A. S. Mourão 《Cell and tissue research》2010,340(3):523-531
Marine sponges (Porifera) display an ancestral type of cell-cell adhesion, based on carbohydrate-carbohydrate interaction.
The aim of the present work was to investigate further details of this adhesion by using, as a model, the in vitro aggregation
of dissociated sponge cells. Our results showed the participation of sulfated polysaccharides in this cell-cell interaction,
as based on the following observations: (1) a variety of sponge cells contained similar sulfated polysaccharides as surface-associated
molecules and as intracellular inclusions; (2) 35S-sulfate metabolic labeling of dissociated sponge cells revealed that the majority (two thirds) of the total sulfated polysaccharide
occurred as a cell-surface-associated molecule; (3) the aggregation process of dissociated sponge cells demanded the active
de novo synthesis of sulfated polysaccharides, which ceased as cell aggregation reached a plateau; (4) the typical well-organized
aggregates of sponge cells, known as primmorphs, contained three cell types showing sulfated polysaccharides on their cell
surface; (5) collagen fibrils were also produced by the primmorphs in order to fill the extracellular spaces of their inner
portion and the external layer surrounding their entire surface. Our data have thus clarified the relevance of sulfated polysaccharides
in this system of in vitro sponge cell aggregation. The molecular basis of this system has practical relevance, since the
culture of sponge cells is necessary for the production of molecules with biotechnological applications. 相似文献
40.
Alberto Biscontin Silvia Casara Stefano Cagnin Lucia Tombolan Angelo Rosolen Gerolamo Lanfranchi Cristiano De Pittà 《BMC molecular biology》2010,11(1):44