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41.
Bizat N Hermel JM Humbert S Jacquard C Créminon C Escartin C Saudou F Krajewski S Hantraye P Brouillet E 《The Journal of biological chemistry》2003,278(44):43245-43253
The role of caspases and calpains in neurodegeneration remains unclear. In this study, we focused on these proteases in a rat model of Huntington's disease using the mitochondrial toxin 3-nitropropionic acid (3NP). Results showed that 3NP-induced death of striatal neurons was preceded by cytochrome c redistribution, transient caspase-9 processing, and activation of calpain, whereas levels of the active/processed form of caspase-3 remained low and were even reduced as compared with control animals. We evidenced here that this decrease in active caspase-3 levels could be attributed to calpain activation. Several observations supported this conclusion. 1) Pharmacological blockade of calpain in 3NP-treated rats increased the levels of endogenous processed caspase-9 and caspase-3. 2) Cell-free extracts prepared from the striatum of 3NP-treated rats degraded in vitro the p34 and p20 subunits of active recombinant caspase-9 and caspase-3, respectively. 3) This degradation of p34 and p20 could be mimicked by purified mu-calpain and was prevented by calpain inhibitors. 4) mu-Calpain produced a loss of the DEVDase (Asp-Glu-Val-Asp) activity of active caspase-3. 5) Western blot analysis and experiments with 35S-radiolabeled caspase-3 showed that mu-calpain cleaved the p20 subunit of active caspase-3 near its catalytic site. 6) mu-Calpain activity was selectively inhibited (IC50 of 100 mum) by a 12 amino acid peptide corresponding to the C terminus of p20. Our results showed that calpain can down-regulate the caspase-9/caspase-3 cell death pathway during neurodegeneration due to chronic mitochondrial defects in vivo and that this effect may involve, at least in part, direct cleavage of the caspase-3 p20 subunit. 相似文献
42.
Data analysis--not data production--is becoming the bottleneck in gene expression research. Data integration is necessary to cope with an ever increasing amount of data, to cross-validate noisy data sets, and to gain broad interdisciplinary views of large biological data sets. New Internet resources may help researchers to combine data sets across different gene expression platforms. However, noise and disparities in experimental protocols strongly limit data integration. A detailed review of four selected studies reveals how some of these limitations may be circumvented and illustrates what can be achieved through data integration. 相似文献
43.
Nezer C Collette C Moreau L Brouwers B Kim JJ Giuffra E Buys N Andersson L Georges M 《Genetics》2003,165(1):277-285
We herein describe the fine mapping of an imprinted QTL with major effect on muscle mass that was previously assigned to distal SSC2p in the pig. The proposed approach exploits linkage disequilibrium in combination with QTL genotyping by marker-assisted segregation analysis. By identifying a haplotype shared by all "Q" chromosomes, we map the QTL to an approximately 250-kb chromosome segment containing INS and IGF2 as the only known paternally expressed genes. This considerably reinforces the candidacy of these genes, justifying their detailed analysis. 相似文献
44.
Menezes CM Kirchgatter K Di Santi SM Savalli C Monteiro FG Paula GA Ferreira EI 《Memórias do Instituto Oswaldo Cruz》2002,97(7):1033-1039
Phenothiazine drugs - fluphenazine, chlorpromazine, methotrimeprazine and trifluoperazine - were evaluated as modulating agents against Brazilian chloroquine-resistant fresh isolates of Plasmodium falciparum. Aiming to simulate therapeutic schedules, chloroquine was employed at the concentration used for sensitive falciparum malaria treatment and anti-psychotic therapeutic concentrations of the phenothiazine drugs were adopted in two-fold serial dilutions. The in vitro microtechnique for drug susceptibility was employed. Unlike earlier reported data, the phenothiazine modulating effect was not observed. However, all the drugs demonstrated intrinsic antiplasmodial activity in concentrations lower than those described in the literature. In addition, IC50 estimates have been shown to be inferior to the usual anti-psychotic therapeutic concentrations. Statistical analysis also suggested an increase in the parasitaemia rate or, even, a predominant antiparasitic effect of phenothiazine over chloroquine when used in combination. 相似文献
45.
46.
Carine Bécamel Nathalie Galéotti Joël Poncet Patrick Jouin Aline Dumuis Joël Bockaert Philippe Marin 《Biological procedures online》2002,4(1):94-104
There is accumulating evidence that membrane-bound receptors interact with many intracellular proteins. Multiprotein complexes
associated with ionotropic receptors have been extensively characterized, but the identification of proteins interacting with
G protein-coupled receptors (GPCRs) has so far only been achieved in a piecemeal fashion, focusing on one or two protein species.
We describe a method based on peptide affinity chromatography, two-dimensional electrophoresis, mass spectrometry and immunoblotting
to identify the components of multiprotein complexes interacting directly or indirectly with intracellular domains of GPCRs
or, more generally, any other membrane-bound receptor. Using this global approach, we have characterized multiprotein complexes
that bind to the carboxy-terminal tail of the 5-hydroxytryptamine type 2C receptor and are important for its subcellular localization
in CNS cells (Bécamel et al., EMBO J., 21(10): 2332, 2002).
Published: December 9, 2002 相似文献
47.
Physical and functional interaction of the Arabidopsis K(+) channel AKT2 and phosphatase AtPP2CA 下载免费PDF全文
Chérel I Michard E Platet N Mouline K Alcon C Sentenac H Thibaud JB 《The Plant cell》2002,14(5):1133-1146
The AKT2 K(+) channel is endowed with unique functional properties, being the only weak inward rectifier characterized to date in Arabidopsis. The gene is expressed widely, mainly in the phloem but also at lower levels in leaf epiderm, mesophyll, and guard cells. The AKT2 mRNA level is upregulated by abscisic acid. By screening a two-hybrid cDNA library, we isolated a protein phosphatase 2C (AtPP2CA) involved in abscisic acid signaling as a putative partner of AKT2. We further confirmed the interaction by in vitro binding studies. The expression of AtPP2CA (beta-glucuronidase reporter gene) displayed a pattern largely overlapping that of AKT2 and was upregulated by abscisic acid. Coexpression of AtPP2CA with AKT2 in COS cells and Xenopus laevis oocytes was found to induce both an inhibition of the AKT2 current and an increase of the channel inward rectification. Site-directed mutagenesis and pharmacological analysis revealed that this functional interaction involves AtPP2CA phosphatase activity. Regulation of AKT2 activity by AtPP2CA in planta could allow the control of K(+) transport and membrane polarization during stress situations. 相似文献
48.
Bady I Zitoun C Guignot L Mithieux G 《American journal of physiology. Endocrinology and metabolism》2002,282(4):E905-E910
This study was conducted to test the hypothesis of the activation of glucose-6-phosphatase (G-6-Pase) in situations where the liver is supposed to sustain high glucose supply, such as during the counterregulatory response to hypoglycemia. Hypoglycemia was induced by insulin infusion in anesthetized rats. Despite hyperinsulinemia, endogenous glucose production (EGP), assessed by [3-(3)H]glucose tracer dilution, was paradoxically not suppressed in hypoglycemic rats. G-6-Pase activity, assayed in a freeze-clamped liver lobe, was increased by 30% in hypoglycemia (P < 0.01 vs. saline-infused controls). Infusion of epinephrine (1 microg x kg(-1) x min(-1)) in normal rats induced a dramatic 80% increase in EGP and a 60% increase in G-6-Pase activity. In contrast, infusion of dexamethasone had no effect on these parameters. Similar insulin-induced hypoglycemia experiments performed in adrenalectomized rats did not induce any stimulation of G-6-Pase. Infusion of epinephrine in adrenalectomized rats restored a stimulation of G-6-Pase similar to that triggered by hypoglycemia in normal rats. These results strongly suggest that specific activatory mechanisms of G-6-Pase take place and contribute to EGP in situations where the latter is supposed to be sustained. 相似文献
49.
Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure 总被引:10,自引:0,他引:10
Cueille C Pidoux E de Vernejoul MC Ventura-Clapier R Garel JM 《Biochemical and biophysical research communications》2002,294(2):340-346
Calcitonin gene-related peptide (CGRP) and adrenomedullin (ADM) are potent vasodilators in humans and improved myocardial ischemia is observed after CGRP administration. Receptors for CGRP and ADM were already identified in heart. Receptor activity-modifying proteins (RAMPs) determine the ligand specificity of the calcitonin receptor-like receptor (CRLR); co-expression of RAMP1 and CRLR results in a CGRP receptor, whereas the association of RAMP2 or RAMP3 with CRLR gives an ADM receptor. As CGRP and ADM may play a beneficial role in heart failure, we investigated whether the CGRP and ADM receptors are upregulated in chronic heart failure. We have used semi-quantitative RT-PCR and Western-blot analysis to detect and quantify the mRNA and the protein of RAMP1 and RAMP3 in both atria and ventricles of failing hearts 6 months after aortic banding in rats. Our results showed for the first time an up-regulation of RAMP1 and RAMP3 mRNAs and proteins in this model of cardiac failure. No change was observed in mRNAs coding for CRLR, RAMP2, RDC1 (canine orphan receptor), and ADM. The present results suggested after congestive heart failure in adult rats, an up-regulation of the CGRP receptor (by an increase in RAMP1 that is associated with CRLR) in atria and ventricles and of ADM receptor (by increased RAMP3 expression that is associated with CRLR) in atria. These findings support a functional role for CGRP and ADM receptors to compensate the chronic heart failure in rats. 相似文献