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101.
Watanabe Y Morita E Fukada Y Doi K Yasui K Kitayama M Nakano T Nakashima K 《PloS one》2008,3(10):e3497
Background
Multiple cellular functions are compromised in amyotrophic lateral sclerosis (ALS). In familial ALS (FALS) with Cu/Zn superoxide dismutase (SOD1) mutations, the mechanisms by which the mutation in SOD1 leads to such a wide range of abnormalities remains elusive.Methodology/Principal Findings
To investigate underlying cellular conditions caused by the SOD1 mutation, we explored mutant SOD1-interacting proteins in the spinal cord of symptomatic transgenic mice expressing a mutant SOD1, SOD1Leu126delTT with a FLAG sequence (DF mice). This gene product is structurally unable to form a functional homodimer. Tissues were obtained from both DF mice and disease-free mice expressing wild-type with FLAG SOD1 (WF mice). Both FLAG-tagged SOD1 and cross-linking proteins were enriched and subjected to a shotgun proteomic analysis. We identified 34 proteins (or protein subunits) in DF preparations, while in WF preparations, interactions were detected with only 4 proteins.Conclusions/Significance
These results indicate that disease-causing mutant SOD1 likely leads to inadequate protein-protein interactions. This could be an early and crucial process in the pathogenesis of FALS. 相似文献102.
Ken Sasaki Jyoti Gaikwad Shuhei Hashiguchi Toshiya Kubota Kazuhisa Sugimura Werner Kremer Hans Robert Kalbitzer Kazuyuki Akasaka 《朊病毒》2008,2(3):118-122
The structure and the dissociation reaction of oligomers PrPoligo from reduced human prion huPrPC(23–231) have been studied by 1H-NMR and tryptophan fluorescence spectroscopy at varying pressure, along with circular dichroism and atomic force microscopy. The 1H-NMR and fluorescence spectral feature of the oligomer is consistent with the notion that the N-terminal residues including all seven Trp residues, are free and mobile, while residues 105∼210, comprising the AGAAAAGA motif and S1-Loop-HelixA-Loop-S2-Loop-HelixC, are engaged in intra- and/or inter-molecular interactions. By increasing pressure to 200 MPa, the oligomers tend to dissociate into monomers which may be identified with PrPC*, a rare metastable form of PrPC stabilized at high pressure (Kachel et al., BMC Struct Biol 6:16). The results strongly suggest that the oligomeric form PrPoligo is in dynamic equilibrium with the monomeric forms via PrPC*, namely huPrPC ⇆ huPrPC* ⇆ huPrPoligo.Key words: human prion, oligomer structure, pressure dissociation, reversible monomer-oligomer transition, circular dichroism, high pressure NMR, atomic force microscopy 相似文献
103.
Two distinct pathways for cyclooxygenase-2 protein degradation 总被引:1,自引:0,他引:1
Mbonye UR Yuan C Harris CE Sidhu RS Song I Arakawa T Smith WL 《The Journal of biological chemistry》2008,283(13):8611-8623
Cyclooxygenases (COX-1 and COX-2) are N-glycosylated, endoplasmic reticulum-resident, integral membrane proteins that catalyze the committed step in prostanoid synthesis. COX-1 is constitutively expressed in many types of cells, whereas COX-2 is usually expressed inducibly and transiently. The control of COX-2 protein expression occurs at several levels, and overexpression of COX-2 is associated with pathologies such as colon cancer. Here we have investigated COX-2 protein degradation and demonstrate that it can occur through two independent pathways. One pathway is initiated by post-translational N-glycosylation at Asn-594. The N-glycosyl group is then processed, and the protein is translocated to the cytoplasm, where it undergoes proteasomal degradation. We provide evidence from site-directed mutagenesis that a 27-amino acid instability motif (27-IM) regulates posttranslational N-glycosylation of Asn-594. This motif begins with Glu-586 8 residues upstream of the N-glycosylation site and ends with Lys-612 near the C terminus at Leu-618. Key elements of the 27-IM include a helix involving residues Glu-586 to Ser-596 with Asn-594 near the end of this helix and residues Leu-610 and Leu-611, which are located in an apparently unstructured downstream region of the 27-IM. The last 16 residues of the 27-IM, including Leu-610 and Leu-611, appear to promote N-glycosylation of Asn-594 perhaps by causing this residue to become exposed to appropriate glycosyl transferases. A second pathway for COX-2 protein degradation is initiated by substrate-dependent suicide inactivation. Suicide-inactivated protein is then degraded. The biochemical steps have not been resolved, but substrate-dependent degradation is not inhibited by proteasome inhibitors or inhibitors of lysosomal proteases. The pathway involving the 27-IM occurs at a constant rate, whereas degradation through the substrate-dependent process is coupled to the rate of substrate turnover. 相似文献
104.
Campa VM Gutiérrez-Lanza R Cerignoli F Díaz-Trelles R Nelson B Tsuji T Barcova M Jiang W Mercola M 《The Journal of cell biology》2008,183(1):129-141
The inability of heart muscle to regenerate by replication of existing cardiomyocytes has engendered considerable interest in identifying developmental or other stimuli capable of sustaining the proliferative capacity of immature cardiomyocytes or stimulating division of postmitotic cardiomyocytes. Here, we demonstrate that reactivation of Notch signaling causes embryonic stem cell–derived and neonatal ventricular cardiomyocytes to enter the cell cycle. The proliferative response of neonatal ventricular cardiomyocytes declines as they mature, such that late activation of Notch triggers the DNA damage checkpoint and G2/M interphase arrest. Notch induces recombination signal-binding protein 1 for Jκ (RBP-Jκ)-dependent expression of cyclin D1 but, unlike other inducers, also shifts its subcellular distribution from the cytosol to the nucleus. Nuclear localization of cyclin D1 is independent of RBP-Jκ. Thus, the influence of Notch on nucleocytoplasmic localization of cyclin D1 is an unanticipated property of the Notch intracellular domain that is likely to regulate the cell cycle in multiple contexts, including tumorigenesis as well as cardiogenesis. 相似文献
105.
Honda K Yamashita S Nakagawa H Sameshima Y Omasa T Kato J Ohtake H 《Applied microbiology and biotechnology》2008,78(5):767-773
Rhodococcus opacus B-4, which has recently been isolated as an organic solvent-tolerant bacterium, stabilized water-in-oil (w/o) emulsions by
inhibition of droplet coalescence when the cells were dispersed in 90% (v/v) organic solvents. Confocal microscopy revealed that many bacterial cells assembled at the interface between oil and water
droplets, though free cells were also detectable at the inside of water droplets. Bacterial cells in the w/o emulsion were
capable of utilizing both a water-soluble (glucose) and an oil-soluble substrate (oleic acid) as an energy source. Availability
of the w/o emulsion as an immobilized cell system in organic solvents was demonstrated using production of indigo from indole
and production of o-cresol from toluene as model conversions. When glucose and oleic acid were simultaneously supplied as energy sources, the
w/o emulsion culture of R. opacus B-4 produced indigo and o-cresol at levels of 0.217 and 2.12 mg ml−1, respectively, by 12 h. 相似文献
106.
Suzuki M Endo N Nakano Y Kato H Kishiro T Asahina K 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2008,178(2):149-156
This study examined the distribution pattern of aquaporin-2 (AQP2), relative medullary thickness (RMT) and urine properties
in the bottlenose dolphin Tursiops
truncatus and Baird’s beaked whale Berardius bairdii. Immunohistochemical studies revealed that AQP2 was localized in the collecting tubules/ducts of both species’ renicules,
as in terrestrial mammals. The collecting ducts with AQP2 were thinner and arranged more densely in the dolphin than in the
whale. RMT values in the renicule were moderate in both species, but were significantly higher in the dolphin (6.0 ± 0.9)
than the whale (4.9 ± 0.7). Urine of the bottlenose dolphin is comparatively concentrated (osmolality: 1715.7 ± 279.4 mOsm kg−1, Na+: 490.1 ± 87.9 mmol l−1, Cl−: 402.7 ± 79.6 mmol l−1, K+: 80.7 ± 25.8 mmol l−1, urea nitrogen: 703.5 ± 253.9 mmol l−1), while urine of the dead Baird’s beaked whale is less concentrated (osmolality: 837.5 ± 293.8 mOsm kg−1, Na+: 192.9 ± 81.5 mmol l−1, Cl−: 159.9 ± 71.4 mmol l−1, K+: 44.3 ± 29.5 mmol l−1, urea nitrogen: 270.7 ± 120.3 mmol l−1). These data suggest it is possible that the differences in these renal morphological features may be related in some way
to the difference in urine composition between the species, although further studies are necessary.
M. Suzuki and N. Endo are equal contributors to this study. 相似文献
107.
Okayama T Kikuchi S Ochiai T Ikoma H Kubota T Ichikawa D Fujiwara H Okamoto K Sakakura C Sonoyama T Kokuba Y Doi Y Tsukita S Bissell DM Otsuji E 《Biochimica et biophysica acta》2008,1782(9):542-548
Hepatic stellate cells (HSCs) respond to injury with a coordinated set of events (termed activation), which includes migration and upregulation of matrix protein production. Cell migration requires an intact actin cytoskeleton that is linked to the plasma membrane by ezrin-radixin-moesin (ERM) proteins. We have previously found that the linker protein in HSCs is exclusively moesin. Here, we describe HSC migration and fibrogenesis in moesin-deficient mice. We developed an acute liver injury model that involved focal thermal denaturation and common bile duct ligation. HSC migration and collagen deposition were assessed by immunohistology and quantitative real-time PCR. Activated HSCs were isolated from wild-type or moesin-deficient mice for direct examination of migration. Activated HSCs from wild-type mice were positive for moesin. Migration of moesin-deficient HSCs was significantly reduced. In a culture assay, 22.1% of normal HSCs migrated across a filter in 36h. In contrast, only 1.3% of activated moesin-deficient HSCs migrated. Collagen deposition around the injury area similarly was reduced in moesin-deficient liver. The linker protein moesin is essential for HSC activation and migration in response to injury. Fibrogenesis is coupled to migration and reduced in moesin-deficient mice. Agents that target moesin may be beneficial for chronic progressive fibrosis. 相似文献
108.
Identification and functional characterization of a novel human and rat riboflavin transporter, RFT1
Yonezawa A Masuda S Katsura T Inui K 《American journal of physiology. Cell physiology》2008,295(3):C632-C641
Absorption of riboflavin is mediated by transporter(s). However, a mammalian riboflavin transporter has yet to be identified. In the present study, the novel human and rat riboflavin transporters hRFT1 and rRFT1 were identified on the basis of our rat kidney mRNA expression database (Horiba N, Masuda S, Takeuchi A, Saito H, Okuda M, Inui K. Kidney Int 66: 29-45, 2004). hRFT1 and rRFT1 cDNAs have an open reading frame encoding 448- and 450-amino acid proteins, respectively, that exhibit 81.1% identity and 96.4% similarity to one another. In addition, an inactive splice variant of hRFT1, hRFT1sv, was also cloned. The hRFT1sv cDNA, which encodes a 167-amino acid protein, retains an intron between exons 2 and 3 of hRFT1. Real-time PCR revealed that the sum of hRFT1 and hRFT1sv mRNAs was expressed strongly in the placenta and small intestine and was detected in all tissues examined. In addition, hRFT1 and hRFT1sv were expressed in human embryonic kidney (HEK)-293 and Caco-2 cells. HEK-293 cells transfected with green fluorescent protein-tagged hRFT1 and rRFT1 exhibited a fluorescent signal in the plasma membrane. Overexpression of hRFT1 and rRFT1, but not hRFT1sv, increased the cellular accumulation of [(3)H]riboflavin. The transfection of small interfering RNA targeting both hRFT1 and hRFT1sv significantly decreased the uptake of [(3)H]riboflavin by HEK-293 and Caco-2 cells. Riboflavin transport is Na(+), potential, and pH independent. Kinetic analyses demonstrated that the Michaelis-Menten constants for the uptake by HEK-293 and Caco-2 cells were 28.1 and 63.7 nM, respectively. We propose that hRFT1 and rRFT1 are novel mammalian riboflavin transporters, which belong to a new mammalian riboflavin transporter family. 相似文献
109.
Phylogeny and distribution of extra-slow-growing Bradyrhizobium japonicum harboring high copy numbers of RSα, RSβ and IS1631 总被引:1,自引:0,他引:1
110.
Summary A newly isolated bacterium, strain TB-135, produces solely D-lactic acid from 1,2-propanediol (1,2-PD). From taxonomical studies, the strain was concluded to belong to the genusPseudomonas. The optimal conditions for the acid production were found to be at 4% 1,2-PD and 0.2% yeast extract, when the strain produced 21mg/ml of the acid of a high optical purity (over 99% e.e.) after 4days of cultivation. Since it was considered that the acid was produced from (R)-(–)-1,2-PD, the molar yield was estimated to be 86%. 相似文献