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71.
Cynthia Brisac Fran?ois Téoulé Arnaud Autret Isabelle Pelletier Florence Colbère-Garapin Catherine Brenner Christophe Lemaire Bruno Blondel 《Journal of virology》2010,84(23):12226-12235
We show that poliovirus (PV) infection induces an increase in cytosolic calcium (Ca2+) concentration in neuroblastoma IMR5 cells, at least partly through Ca2+ release from the endoplasmic reticulum lumen via the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels. This leads to Ca2+ accumulation in mitochondria through the mitochondrial Ca2+ uniporter and the voltage-dependent anion channel (VDAC). This increase in mitochondrial Ca2+ concentration in PV-infected cells leads to mitochondrial dysfunction and apoptosis.Poliovirus (PV), the prototype member of the Picornaviridae family, is the etiological agent of paralytic poliomyelitis (26, 27). This acute human disease of the central nervous system results from the destruction of motor neurons associated with PV replication. In PV-infected mice, motor neurons die through apoptosis (16). However, the mechanisms involved are poorly understood (5).Apoptosis is an active cell death process triggered by various stimuli, including viral infections (18). This process leads to DNA fragmentation and is triggered by two main pathways (22): (i) the extrinsic pathway, mediated by the activation of cell surface death receptors such as Fas/CD95, and (ii) the intrinsic pathway, characterized notably by mitochondrial membrane permeabilization (MMP). In many models, this process implies a loss of mitochondrial transmembrane potential (Δψm) and the release of proapoptotic molecules, including cytochrome c, from the mitochondrial intermembrane space into the cytosol. The apoptotic program initiated by PV infection has been shown to involve mitochondrial dysfunction in several cell lines (2-4, 17).The intrinsic pathway also can originate from the endoplasmic reticulum (ER) (30). The ER participates in protein synthesis and folding, cellular responses to stress, and intracellular calcium (Ca2+) homeostasis. Nevertheless, under stress conditions, it may induce apoptosis via several different mechanisms, one of which involves ER cross-talk with mitochondria, mediated by Ca2+ release from ER stores through the inositol 1,4,5-triphosphate receptor (IP3R) and ryanodine receptor (RyR) channels (7, 12, 15). Several recent studies have identified Ca2+ signaling as a key cellular target for viral infection (for a review, see reference 8). Upon PV infection, cells display an increase in cytosolic Ca2+ concentration (20). Phospholipase C also is activated, leading to an increase in IP3 concentration in PV-infected cells (19), potentially accounting for the observed increase in cytosolic Ca2+ concentration. However, the role of Ca2+ efflux from the ER in PV-induced apoptosis has yet to be studied.Here, we postulated that an increase in cytosolic Ca2+ following PV infection can have an impact on cell fate and investigated the cellular response in terms of mitochondrial function and apoptosis in neuroblastoma IMR5 cells. 相似文献
72.
Patricia Bernal Sandrine Lemaire Mariana G. Pinho Shahriar Mobashery Jason Hinds Peter W. Taylor 《The Journal of biological chemistry》2010,285(31):24055-24065
Epicatechin gallate (ECg) sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to oxacillin and other β-lactam agents; it also reduces the secretion of virulence-associated proteins, prevents biofilm formation, and induces gross morphological changes in MRSA cells without compromising the growth rate. MRSA is resistant to oxacillin because of the presence of penicillin-binding protein 2a (PBP2a), which allows peptidoglycan synthesis to continue after oxacillin-mediated acylation of native PBPs. We show that ECg binds predominantly to the cytoplasmic membrane (CM), initially decreasing the fluidity of the bilayer, and induces changes in gene expression indicative of an attempt to preserve and repair a compromised cell wall. On further incubation, the CM is reorganized; the amount of lysylphosphatidylglycerol is markedly reduced, with a concomitant increase in phosphatidylglycerol, and the proportion of branched chain fatty acids increases, resulting in a more fluid structure. We found no evidence that ECg modulates the enzymatic activity of PBP2a through direct binding to the protein but determined that PBP2 is delocalized from the FtsZ-anchored cell wall biosynthetic machinery at the septal division site following intercalation into the CM. We argue that many features of the ECg-induced phenotype can be explained by changes in the fluid dynamics of the CM. 相似文献
73.
Sourdeval M Lemaire C Deniaud A Taysse L Daulon S Breton P Brenner C Boisvieux-Ulrich E Marano F 《Apoptosis : an international journal on programmed cell death》2006,11(9):1545-1559
In the present study, the toxicity of yperite, SM, and its structural analogue mechlorethamine, HN2, was investigated in a
human bronchial epithelial cell line 16HBE. Cell detachment was initiated by caspase-2 activation, down-regulation of Bcl-2
and loss of mitochondrial membrane potential. Only in detached cells, mustards induced apoptosis associated with increase
in p53 expression, Bax activation, decrease in Bcl-2 expression, opening of the mitochondrial permeability transition pore,
release of cytochrome c, caspase-2, -3, -8, -9 and -13 activation and DNA fragmentation. Apoptosis, occurring only in detached cells, could be recognized
as anoikis and the mitochondrion, involved both in cell detachment and subsequent cell death, appears to be a crucial checkpoint.
Based on our understanding of the apoptotic pathway triggered by mustards, we demonstrated that inhibition of the mitochondrial
pathway by ebselen, melatonin and cyclosporine A markedly prevented mustard-induced anoikis, pointing to these drugs as interesting
candidates for the treatment of mustard-induced airway epithelial lesions.
This work was support by the Délégation Générale pour l’Armement (D.G.A./D.S.P. No. 95-151). A. Deniaud received a fellowship
from Ligue contre le Cancer. C. Brenner is supported by the Association pour la Recherche sur le Cancer (ARC). The authors
are grateful to D.C. Gruenert for providing us with the human bronchial epithelial cell line. 相似文献
74.
The synthesis, structure, and magnetic properties of a dinuclear Co(II) complex of a tridentate verdazyl radical are presented. The reaction of a tetrazane containing a 4,6-bis(2-pyridyl)-pyrimid-2-yl substituent with cobalt chloride hexahydrate in aerated solution leads to in situ oxidation of the tetrazane to a verdazyl radical which is coordinated to Co(II) in a tridentate manner. The second tridentate coordination site of the verdazyl remains vacant. The crystal structure reveals the complex to be dimeric, with the cobalt ions linked by two bridging chlorides. The structure of Co2Cl2 core is highly asymmetric, with two short (2.3317 Å) and two long (2.744 Å) Co-Cl bonds. There are relatively short intermolecular contacts between coordinated verdazyl radicals in the solid state. Magnetic susceptibility data from 2 to 300 K suggest intramolecular ferromagnetic interactions, and modeling of the high-temperature data produced a best fit with JCo-verdazyl of +20 cm−1. 相似文献
75.
RP Tucker K Drabikowski JF Hess J Ferralli R Chiquet-Ehrismann JC Adams 《BMC evolutionary biology》2006,6(1):60-17
Background
Tenascins are a family of glycoproteins found primarily in the extracellular matrix of embryos where they help to regulate cell proliferation, adhesion and migration. In order to learn more about their origins and relationships to each other, as well as to clarify the nomenclature used to describe them, the tenascin genes of the urochordate Ciona intestinalis, the pufferfish Tetraodon nigroviridis and Takifugu rubripes and the frog Xenopus tropicalis were identified and their gene organization and predicted protein products compared with the previously characterized tenascins of amniotes. 相似文献76.
Background
Trichomonosis caused by Trichomonas vaginalis is the number one, non-viral sexually transmitted disease (STD) that affects more than 250 million people worldwide. Immunoglobulin A (IgA) has been implicated in resistance to mucosal infections by pathogens. No reports are available of IgA-reactive proteins and the role, if any, of this class of antibody in the control of this STD. The availability of an IgA monoclonal antibody (mAb) immunoreactive to trichomonads by whole cell (WC)-ELISA prompted us to characterize the IgA-reactive protein of T. vaginalis. 相似文献77.
Salmon-Chemin L Lemaire A De Freitas S Deprez B Sergheraert C Davioud-Charvet E 《Bioorganic & medicinal chemistry letters》2000,10(7):631-635
Solid- and solution-phase parallel syntheses of 1,4-naphthoquinones (1,4-NQ) are described. A library of 1360 amides was constructed from the combination of 12 newly synthesised 1,4-NQ carboxylic acid and 120 amines, and was screened for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi. The most active hits from a primary screening were re-synthesised and confirmed. This approach proves that it is possible to design potent and highly specific TcTR inhibitors deriving from menadione, juglone and plumbagin. 相似文献
78.
Beuneu C Auger R Löffler M Guissani A Lemaire G Lepoivre M 《Free radical biology & medicine》2000,28(8):1206-1213
Dihydroorotate dehydrogenase (DHODH) catalyzes the oxidation of dihydroorotate to orotate in the pyrimidine biosynthesis pathway. It is functionally connected to the respiratory chain, delivering electrons to ubiquinone. We report here that inhibition of cytochrome c oxidase by nitric oxide (NO) indirectly inhibits DHODH activity. In digitonin-permeabilized cells, DEA/NO, a chemical NO donor, induced a dramatic decrease in DHO-dependent O(2) consumption. The inhibition was reversible and more pronounced at low O(2) concentration; it was correlated with a decrease in orotate synthesis. Since orotate is the precursor of all pyrimidine nucleotides, indirect inhibition of DHODH by NO may significantly contribute to NO-dependent cytotoxicity. 相似文献
79.
Collodoro M Lemaire P Eppe G Bertrand V Dobson R Mazzucchelli G Widart J De Pauw E De Pauw-Gillet MC 《Journal of Proteomics》2012,75(14):4555-4569
This paper reports the identification of biomarkers resulting from the exposure of MCF-7/BOS cells to 17β-estradiol (E(2)). The biomarkers were identified using 2 independent and complementary techniques, 2-D DIGE/MALDI-TOF peptide mass fingerprint, and 2-D UPLC-ESI MS/MS. They were identified from the cytosolic fractions of cells treated for 24h with mitogenic concentrations of 1, 30 and 500 pM of 17β-estradiol. Five biomarkers were up-regulated proteins, namely HSP 74, EF2, FKBP4, EF1 and GDIB and one was a down-regulated protein, namely K2C8. Three of these proteins, EF2, FKBP4 and K2C8 are implicated in a network centered on the estrogen receptors ESR1 and ESR2 as well as on AKT1. After the discovery phase, three biomarkers were selected to test the presence of estrogens using selected reaction monitoring (SRM). They were monitored using SRM after incubation of MCF-7/BOS in the presence of E(2) for confirmation or selected xenoestrogens. Daidzein, coumestrol and enterolactone induced an up-regulation of EF2 and FKPB4 proteins, while tamoxifen and resveratrol induced a down-regulation. The exposure of all phytoestrogens induced the down-regulation of K2C8. These markers form a preliminary molecular signature that can be used when testing the estrogenic activity of xenobiotics, either pure or in mixtures. 相似文献
80.
R Pardoux S Sauge-Merle D Lemaire P Delangle L Guilloreau JM Adriano C Berthomieu 《PloS one》2012,7(8):e41922
To improve our understanding of uranium toxicity, the determinants of uranyl affinity in proteins must be better characterized. In this work, we analyzed the contribution of a phosphoryl group on uranium binding affinity in a protein binding site, using the site 1 EF-hand motif of calmodulin. The recombinant domain 1 of calmodulin from A. thaliana was engineered to impair metal binding at site 2 and was used as a structured template. Threonine at position 9 of the loop was phosphorylated in vitro, using the recombinant catalytic subunit of protein kinase CK2. Hence, the T9TKE12 sequence was substituted by the CK2 recognition sequence TAAE. A tyrosine was introduced at position 7, so that uranyl and calcium binding affinities could be determined by following tyrosine fluorescence. Phosphorylation was characterized by ESI-MS spectrometry, and the phosphorylated peptide was purified to homogeneity using ion-exchange chromatography. The binding constants for uranyl were determined by competition experiments with iminodiacetate. At pH 6, phosphorylation increased the affinity for uranyl by a factor of ∼5, from Kd = 25±6 nM to Kd = 5±1 nM. The phosphorylated peptide exhibited a much larger affinity at pH 7, with a dissociation constant in the subnanomolar range (Kd = 0.25±0.06 nM). FTIR analyses showed that the phosphothreonine side chain is partly protonated at pH 6, while it is fully deprotonated at pH 7. Moreover, formation of the uranyl-peptide complex at pH 7 resulted in significant frequency shifts of the νas(P-O) and νs(P-O) IR modes of phosphothreonine, supporting its direct interaction with uranyl. Accordingly, a bathochromic shift in νas(UO2)2+ vibration (from 923 cm−1 to 908 cm−1) was observed upon uranyl coordination to the phosphorylated peptide. Together, our data demonstrate that the phosphoryl group plays a determining role in uranyl binding affinity to proteins at physiological pH. 相似文献