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861.
862.
Fazi B Melino S Di Sano F Cicero DO Piacentini M Paci M 《Biochemical and biophysical research communications》2006,342(3):881-886
Reticulons (RTNs) are endoplasmic reticulum-associated proteins widely distributed in plants, yeast, and animals. They are characterized by unique N-terminal parts and a common 200 amino acid C-terminal domain containing two long hydrophobic sequences. Despite their implication in many cellular processes, their molecular structure and function are still largely unknown. In this study, the reticulon family member RTN-1C has been expressed and purified in Escherichia coli and its molecular structure has been analysed by fluorescence and CD spectroscopy in different detergents in order to obtain a good solubility and a relative stability. The isotopically enriched protein has been also produced to perform structural studies by NMR spectroscopy. The preliminary results obtained showed that RTN-1C protein possesses helical transmembrane segments when a membrane-like environment is produced by detergents. Moreover, fluorescence experiments indicated the exposure of tryptophan side chains as predicted by structure prediction programs. We also produced the isotopically labelled protein and the procedure adopted allowed us to plan future NMR studies to investigate the biochemical behaviour of reticulon-1C and of its peptides spanning out from the membrane. 相似文献
863.
de Oliveira JS Zaharenko AJ de Freitas JC Konno K de Andrade SA Portaro FC Richardson M Sant'anna OA Tambourgi DV 《Biochimica et biophysica acta》2006,1760(3):453-461
Two cationic proteins, C1 and C3, were purified to homogeneity from the hemolytic fraction of the venom of Bunodosoma caissarum sea anemone. The purification processes employed gel filtration followed by ion exchange chromatography, being the purity and molecular mass confirmed by SDS-PAGE and mass spectrometry. Protein C1 represented the second major peak of the hemolytic fraction and was previously believed to be a cytolysin belonging to a new class of hemolysins. The C1 protein has a molecular mass of 15495 Da and was assayed for hemolysis, PLA2 activity and acute toxicity in crabs and mice, showing no activity in these assays. It has an amino terminal with no similarity to all known hemolysins and, therefore, should not be considered a toxin, being its function completely unknown. The protein C3 (19757 Da), that also lacks PLA2 activity, was recognized by antiserum against Eqt II and presented high hemolytic activity to human erythrocytes (ED50 of 0.270 microg/ml), being named Caissarolysin I (Bcs I). Its activity was inhibited by pre-incubation with sphingomyelin (SM) and also when in presence of erythrocytes pre-treated with the SMase P2, a phospholipase D from the brown spider Loxosceles intermedia, indicating that SM is the main target of Bcs I. Caissarolysin I is the first hemolysin purified from a sea anemone belonging to the genus Bunodosoma and belongs to the Actinoporin family of sea anemone hemolysins. 相似文献
864.
van der Hoogt CC Berbée JF Espirito Santo SM Gerritsen G Krom YD van der Zee A Havekes LM van Dijk KW Rensen PC 《Biochimica et biophysica acta》2006,1761(2):213-220
We have recently shown that the predominant hypertriglyceridemia in human apolipoprotein C1 (APOC1) transgenic mice is mainly explained by apoCI-mediated inhibition of the lipoprotein lipase (LPL)-dependent triglyceride (TG)-hydrolysis pathway. Since the very-low-density lipoprotein receptor (VLDLr) and apoCIII are potent modifiers of LPL activity, our current aim was to study whether the lipolysis-inhibiting action of apoCI would be dependent on the presence of the VLDLr and apoCIII in vivo. Hereto, we employed liver-specific expression of human apoCI by using a novel recombinant adenovirus (AdAPOC1). In wild-type mice, moderate apoCI expression leading to plasma human apoCI levels of 12-33 mg/dl dose-dependently and specifically increased plasma TG (up to 6.6-fold, P < 0.001), yielding the same hypertriglyceridemic phenotype as observed in human APOC1 transgenic mice. AdAPOC1 still increased plasma TG in vldlr(-/-) mice (4.1-fold, P < 0.001) and in apoc3(-/-) mice (6.8-fold, P < 0.001) that were also deficient for the low-density lipoprotein receptor (LDLr) and LDLr-related protein (LRP) or apoE, respectively. Thus, irrespective of receptor-mediated remnant clearance by the liver, liver-specific expression of human apoCI causes hypertriglyceridemia in the absence of the VLDLr and apoCIII. We conclude that apoCI is a powerful and direct inhibitor of LPL activity independent of the VLDLr and apoCIII. 相似文献
865.
Differences in resolution of mwr-containing plasmid dimers mediated by the Klebsiella pneumoniae and Escherichia coli XerC recombinases: potential implications in dissemination of antibiotic resistance genes 下载免费PDF全文
Bui D Ramiscal J Trigueros S Newmark JS Do A Sherratt DJ Tolmasky ME 《Journal of bacteriology》2006,188(8):2812-2820
Xer-mediated dimer resolution at the mwr site of the multiresistance plasmid pJHCMW1 is osmoregulated in Escherichia coli containing either the Escherichia coli Xer recombination machinery or Xer recombination elements from K. pneumoniae. In the presence of K. pneumoniae XerC (XerC(Kp)), the efficiency of recombination is lower than that in the presence of the E. coli XerC (XerC(Ec)) and the level of dimer resolution is insufficient to stabilize the plasmid, even at low osmolarity. This lower efficiency of recombination at mwr is observed in the presence of E. coli or K. pneumoniae XerD proteins. Mutagenesis experiments identified a region near the N terminus of XerC(Kp) responsible for the lower level of recombination catalyzed by XerC(Kp) at mwr. This region encompasses the second half of the predicted alpha-helix B and the beginning of the predicted alpha-helix C. The efficiencies of recombination at other sites such as dif or cer in the presence of XerC(Kp) or XerC(Ec) are comparable. Therefore, XerC(Kp) is an active recombinase whose action is impaired on the mwr recombination site. This characteristic may result in restriction of the host range of plasmids carrying this site, a phenomenon that may have important implications in the dissemination of antibiotic resistance genes. 相似文献
866.
Anna Stochmal Iwona Kowalska Bogdan Janda Angela Perrone Sonia Piacente Wiesaw Oleszek 《Phytochemistry》2009,70(10):1272-1276
Three phenolic glycosides 5-O-{[5′′-O-E-(4′′′-O-threo-guaiacylglycerol)-feruloyl]-β-apiofuranosyl-(1→2)-β-xylopyranosyl} gentisic acid, 5-O-[(5′′-O-vanilloyl)-β-apiofuranosyl-(1→2)-β-xylopyranosyl] gentisic acid and 1-O-[E-(4′′′-O-threo-guaiacylglycerol)-feruloyl]-3-O-β-galacturonopyranosyl glycerol were isolated and identified from the roots of Medicago truncatula together with four known 5-O-β-xylopyranosyl gentisic acid, vicenin-2, hovetrichoside C and pterosupin identified for the first time in this species. Structural elucidation was carried out on the basis of UV, mass, 1H and 13C NMR spectral data. 相似文献
867.
868.
Ruslan Dorfman Weili Li Lei Sun Fan Lin Yongqian Wang Andrew Sandford Peter D. Paré Karen McKay Hana Kayserova Tereza Piskackova Milan Macek Kamila Czerska Dorota Sands Harm Tiddens Sonia Margarit Gabriela Repetto Marci K. Sontag Frank J. Accurso Scott Blackman Garry R. Cutting Lap-Chee Tsui Mary Corey Peter Durie Julian Zielenski Lisa J. Strug 《Human genetics》2009,126(6):763-778
Cystic fibrosis (CF) is a monogenic disease due to mutations in the CFTR gene. Yet, variability in CF disease presentation is presumed to be affected by modifier genes, such as those recently demonstrated for the pulmonary aspect. Here, we conduct a modifier gene study for meconium ileus (MI), an intestinal obstruction that occurs in 16–20% of CF newborns, providing linkage and association results from large family and case–control samples. Linkage analysis of modifier traits is different than linkage analysis of primary traits on which a sample was ascertained. Here, we articulate a source of confounding unique to modifier gene studies and provide an example of how one might overcome the confounding in the context of linkage studies. Our linkage analysis provided evidence of a MI locus on chromosome 12p13.3, which was segregating in up to 80% of MI families with at least one affected offspring (HLOD = 2.9). Fine mapping of the 12p13.3 region in a large case–control sample of pancreatic insufficient Canadian CF patients with and without MI pointed to the involvement of ADIPOR2 in MI (p = 0.002). This marker was substantially out of Hardy–Weinberg equilibrium in the cases only, and provided evidence of a cohort effect. The association with rs9300298 in the ADIPOR2 gene at the 12p13.3 locus was replicated in an independent sample of CF families. A protective locus, using the phenotype of no-MI, mapped to 4q13.3 (HLOD = 3.19), with substantial heterogeneity. A candidate gene in the region, SLC4A4, provided preliminary evidence of association (p = 0.002), warranting further follow-up studies. Our linkage approach was used to direct our fine-mapping studies, which uncovered two potential modifier genes worthy of follow-up. 相似文献
869.
Nicoletta Bodrato Luisa Franco Chiara Fresia Lucrezia Guida Cesare Usai Annalisa Salis Iliana Moreschi Chiara Ferraris Claudia Verderio Giovanna Basile Santina Bruzzone Sonia Scarf�� Antonio De Flora Elena Zocchi 《The Journal of biological chemistry》2009,284(22):14777-14787
Abscisic acid (ABA) is a phytohormone regulating important functions in
higher plants, notably responses to abiotic stress. Recently, chemical or
physical stimulation of human granulocytes was shown to induce production and
release of endogenous ABA, which activates specific cell functions. Here we
provide evidence that ABA stimulates several functional activities of the
murine microglial cell line N9 (NO and tumor necrosis factor-α
production, cell migration) through the second messenger cyclic ADP-ribose and
an increase of intracellular calcium. ABA production and release occur in N9
cells stimulated with bacterial lipopolysaccharide, phorbol myristate acetate,
the chemoattractant peptide f-MLP, or β-amyloid, the primary plaque
component in Alzheimer disease. Finally, ABA priming stimulates N9 cell
migration toward β-amyloid. These results indicate that ABA is a
pro-inflammatory hormone inducing autocrine microglial activation, potentially
representing a new target for anti-inflammatory therapies aimed at limiting
microglia-induced tissue damage in the central nervous system.Microglial cells are the monocyte/macrophage equivalent of the central
nervous system and represent the first line of defense in the brain, by
removing infectious agents and damaged cells
(1). Microglia can also release
a variety of trophic factors and cytokines able to regulate the communication
between neuronal and other glial cells and can contribute to tissue repair and
neuroprotection
(2–4).
Pathologic microglial activation, however, confers neurotoxic properties to
these cells, thereby causing neuronal degeneration
(5). Excessive activation of
microglia, under conditions of chronic inflammation, can contribute to the
pathogenesis of neurodegenerative diseases, such as multiple sclerosis and
Alzheimer and Parkinson diseases, by producing and releasing a number of
potentially cytotoxic substances, including pro-inflammatory cytokines and NO
(4,
6–8).
Therefore, identification of the molecular mechanisms underlying microglial
activation might lead to the development of new anti-inflammatory drugs for
the treatment of these diseases.Abscisic acid
(ABA)2 is a plant
hormone regulating important biological functions in higher plants, including
response to abiotic stress, control of stomatal closure, regulation of seed
dormancy, and germination (9).
Recently, ABA was shown to behave as an endogenous pro-inflammatory hormone in
human granulocytes (10),
stimulating several functional activities of these cells (migration,
phagocytosis, reactive oxygen species, and NO production) through a signaling
cascade that involves a protein kinase A-mediated ADP-ribosyl cyclase
phosphorylation and consequent overproduction of the universal Ca2+
mobilizer cyclic ADP-ribose (cADPR)
(11). This mechanism leads to
an increase of the intracellular Ca2+ concentration, which is
ultimately responsible for granulocyte activation
(10).The facts that microglial cells play a defensive role in the central
nervous system similar to that of granulocytes in other tissues and that cADPR
has been described as the second messenger involved in the activation of
microglia induced by lipopolysaccharide (LPS)
(12) prompted us to
investigate the effect of ABA in these cells.Indeed, exogenous ABA, at concentrations ranging from 250 nm to
20 μm, elicits functional activation of murine N9 cells,
stimulating TNF-α release and cell migration through activation of the
ADP-ribosyl cyclase CD38 and overproduction of cADPR. Moreover, N9 cells
produce and release ABA when stimulated with LPS, amyloid β-peptide
(βA), phorbol myristate acetate (PMA), or the chemoattractant peptide
f-MLP. These results indicate that ABA behaves as an endogenous,
pro-inflammatory hormone in murine microglia and provide a new target for
future investigations into the role of this hormone in inflammatory and
degenerative diseases of the central nervous system accompanied by microglial
activation. 相似文献
870.
Sandra Steiger Sonia Whitlow Klaus Peschke & Josef K. Müller 《Ethology : formerly Zeitschrift fur Tierpsychologie》2009,115(2):178-185
The multicomponent nature of chemical cues and signals are not very well understood. One reason for the often found complexity of chemical blends might be that they provide multiple messages. Burying beetles which use vertebrate carcasses as food for their larvae and defend these carcasses against inter- and intraspecific competitors are able to recognise the sex and breeding status of conspecifics. Studies have shown that the chemical composition of cuticular lipids is correlated with sex and breeding status, but there is no definitive evidence that these chemicals function in recognition. In the present study, we performed behavioural bioassays to directly asses the role of chemical cues in the recognition system of the burying beetle Nicrophorus vespilloides . After finding a carcass, females were more tolerant of dead males than of females. The behaviour was reversed when a solvent extract from the opposite sex was applied. An earlier experiment had shown that females breeding on a carcass treat non-breeding males more aggressively than breeding ones. In the present study, we could trigger the same dichotomous behaviours by presenting a single elytron from a breeding and a non-breeding beetle. In an additional experiment, females tolerated the elytra of non-breeding beetles if we had first applied an extract from a breeding beetle to these elytra. Our study is the first behavioural proof that female burying beetles obtain multiple information from chemical cues. 相似文献