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991.
992.
Hoefs SJ Dieteren CE Distelmaier F Janssen RJ Epplen A Swarts HG Forkink M Rodenburg RJ Nijtmans LG Willems PH Smeitink JA van den Heuvel LP 《American journal of human genetics》2008,82(6):1306-1315
Mitochondrial isolated complex I deficiency is the most frequently encountered OXPHOS defect. We report a patient with an isolated complex I deficiency expressed in skin fibroblasts as well as muscle tissue. Because the parents were consanguineous, we performed homozygosity mapping to identify homozygous regions containing candidate genes such as NDUFA2 on chromosome 5. Screening of this gene on genomic DNA revealed a mutation that interferes with correct splicing and results in the skipping of exon 2. Exon skipping was confirmed on the mRNA level. The mutation in this accessory subunit causes reduced activity and disturbed assembly of complex I. Furthermore, the mutation is associated with a mitochondrial depolarization. The expression and activity of complex I and the depolarization was (partially) rescued with a baculovirus system expressing the NDUFA2 gene. 相似文献
993.
van Genderen HO Kenis H Hofstra L Narula J Reutelingsperger CP 《Biochimica et biophysica acta》2008,1783(6):953-963
In normal healthy cells phosphatidylserine is located in the inner leaflet of the plasma membrane. However, on activated platelets, dying cells and under specific circumstances also on various types of viable leukocytes phosphatidylserine is actively externalized to the outer leaflet of the plasma membrane. Annexin A5 has the ability to bind in a calcium-dependent manner to phosphatidylserine and to form a membrane-bound two-dimensional crystal lattice. Based on these abilities various functions for extracellular annexin A5 on the phosphatidylserine-expressing plasma membrane have been proposed. In this review we describe possible mechanisms for externalization of annexin A5 and various processes in which extracellular annexin A5 may play a role such as blood coagulation, apoptosis, phagocytosis and formation of plasma membrane-derived microparticles. We further highlight the recent discovery of internalization of extracellular annexin A5 by phosphatidylserine-expressing cells. 相似文献
994.
Impaired routing of wild type FXYD2 after oligomerisation with FXYD2-G41R might explain the dominant nature of renal hypomagnesemia 总被引:1,自引:0,他引:1
Cairo ER Friedrich T Swarts HG Knoers NV Bindels RJ Monnens LA Willems PH De Pont JJ Koenderink JB 《Biochimica et biophysica acta》2008,1778(2):398-404
Autosomal dominant renal hypomagnesemia, associated with hypocalciurea, has been linked to a G to A mutation at nucleotide position 121 in the FXYD2 gene, resulting in the substitution of Gly with Arg at residue 41 of the protein. FXYD2, also called the Na,K-ATPase gamma-subunit, binds to Na,K-ATPase and influences its cation affinities. In this paper, we provide evidence for the molecular mechanism underlying the dominant character of the disorder. Co-immunoprecipitation experiments using tagged FXYD2 proteins demonstrated that wild type FXYD2 proteins oligomerise. Moreover, FXYD2-G41R also shows oligomerisation with itself and with the wild type protein. In the case of FXYD2-G41R, however, formation of homo-oligomers was prevented by addition of DTT or introduction of the C52A mutation. Finally, we demonstrated that artificial glycosylation of the wild type FXYD2 is reduced when co-expressed with FXYD2-G41R. These data indicate that binding of FXYD2-G41R to wild type FXYD2 subunit might abrogate the routing of wild type FXYD2 to the plasma membrane thus causing the dominant nature of this mutation. 相似文献
995.
Baldewijns MM van Vlodrop IJ Schouten LJ Soetekouw PM de Bruïne AP van Engeland M 《Biochimica et biophysica acta》2008,1785(2):133-155
Renal cell carcinoma (RCC) is not a single disease, but comprises a group of tumors of renal epithelial origin, each with a different histology, displaying a different clinical course and caused by different genetic alterations. Since cure rates are inversely associated with stage and response to the available treatment regimes is limited to a subgroup of patients, diagnostic methods facilitating early detection and new therapeutic modalities are necessary. Increased knowledge of the underlying pathophysiology of RCC has resulted in the identification of genetic alterations involved in renal cell cancer carcinogenesis. Promising agents to target these pathways, especially the angiogenesis pathway, are being developed, some of which are already standard of care. In addition to genetics, knowledge on epigenetics in the process of renal tumorigenesis has been significantly increased in the last decades. Epigenetics will play an increasing role in the development of new therapeutic modalities and may deliver new prognostic and early diagnostic markers. In this review we discuss the background of RCC and the clinical applications of RCC genetics and epigenetics. 相似文献
996.
Ulfman LH Kamp VM van Aalst CW Verhagen LP Sanders ME Reedquist KA Buitenhuis M Koenderman L 《Journal of immunology (Baltimore, Md. : 1950)》2008,180(8):5512-5519
Although much progress has been made in understanding the molecular mechanisms underlying agonist-induced "inside-out" activation of integrins, little is known about how basal levels of integrin function are maintained. This is particularly important for nonactivated eosinophils, where intermediate activation of alpha(4)beta(1) integrin supports recruitment to endothelial cells under flow conditions. Depletion of intracellular Ca(2+) and pharmacological inhibition of phospholipase C (but not other intracellular signaling molecules, including PI3K, ERK1/2, p38 MAPK, and tyrosine kinase activity) abrogated basal alpha(4) integrin activity in nonactivated eosinophils. Basal alpha(4) integrin activation was associated with activation of the small GTPase Rap1, a known regulator of agonist-induced integrin function. Basal Rap activation was dependent upon phospholipase C, but not intracellular Ca(2+). However, depletion of intracellular Ca(2+) in CD34(+) hematopoietic progenitor cells abolished RapV12-mediated induction of alpha(4) integrin activity. Thus, residual Rap activity or constitutively active Rap activity in Ca(2+)-depleted cells is not sufficient to induce alpha(4) integrin activation. These data suggest that activation of functional alpha(4) integrin activity in resting eosinophils is mediated by Rap1 provided that the intracellular-free Ca(2+) is at a normal homeostatic concentration. 相似文献
997.
Bakema JE Bakker A de Haij S Honing H Bracke M Koenderman L Vidarsson G van de Winkel JG Leusen JH 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(6):4080-4088
To achieve a correct cellular immune response toward pathogens, interaction between FcR and their ligands must be regulated. The Fc receptor for IgA, FcalphaRI, is pivotal for the inflammatory responses against IgA-opsonized pathogens. Cytokine-induced inside-out signaling through the intracellular FcalphaRI tail is important for FcalphaRI-IgA binding. However, the underlying molecular mechanism governing this process is not well understood. In this study, we report that PP2A can act as a molecular switch in FcalphaRI activation. PP2A binds to the intracellular tail of FcalphaRI and, upon cytokine stimulation, PP2A becomes activated. Subsequently, FcalphaRI is dephosphorylated on intracellular Serine 263, which we could link to receptor activation. PP2A inhibition, in contrast, decreased FcalphaRI ligand binding capacity in transfected cells but also in eosinophils and monocytes. Interestingly, PP2A activity was found crucial for IgA-mediated binding and phagocytosis of Neisseria meningitidis. The present findings demonstrate PP2A involvement as a molecular mechanism for FcalphaRI ligand binding regulation, a key step in initiating an immune response. 相似文献
998.
Bleunven C Treves S Jinyu X Leo E Ronjat M De Waard M Kern G Flucher BE Zorzato F 《The Biochemical journal》2008,411(2):343-349
SRP-27 (sarcoplasmic reticulum protein of 27 kDa) is a newly identified integral membrane protein constituent of the skeletal muscle SR (sarcoplasmic reticulum). We identified its primary structure from cDNA clones isolated from a mouse skeletal muscle cDNA library. ESTs (expressed sequence tags) of SRP-27 were found mainly in cDNA libraries from excitable tissues of mouse. Western blot analysis confirmed the expression of SRP-27 in skeletal muscle and, to a lower extent, in heart and brain. Mild trypsin proteolysis combined with primary-structure prediction analysis suggested that SRP-27 has four transmembrane-spanning alpha helices and its C-terminal domain faces the cytoplasmic side of the endo(sarco)plasmic reticulum. The expression of SRP-27 is higher in fast twitch skeletal muscles compared to slow twitch muscles and peaks during the first month of post-natal development. High-resolution immunohistochemistry and Western blot analysis of subcellular fractions indicated that SRP-27 is distributed in both longitudinal tubules and terminal cisternae of the SR, as well as in the perinuclear membrane systems and the nuclear envelope of myotubes and adult fibres. SRP-27 co-sediments with the RyR (ryanodine receptor) macromolecular complex in high-salt sucrose-gradient centrifugation, and is pulled-down by anti-RyR as well as by maurocalcin, a well characterized RyR modulator. Our results indicate that SRP-27 is part of a SR supramolecular complex, suggesting the involvement of SRP-27 in the structural organization or function of the molecular machinery underlying excitation-contraction coupling. 相似文献
999.
Induction of systemic resistance in tomato by N-acyl-L-homoserine lactone-producing rhizosphere bacteria 总被引:2,自引:0,他引:2
Schuhegger R Ihring A Gantner S Bahnweg G Knappe C Vogg G Hutzler P Schmid M Van Breusegem F Eberl L Hartmann A Langebartels C 《Plant, cell & environment》2006,29(5):909-918
N-acyl-L-homoserine lactone (AHL) signal molecules are utilized by Gram-negative bacteria to monitor their population density (quorum sensing) and to regulate gene expression in a density-dependent manner. We show that Serratia liquefaciens MG1 and Pseudomonas putida IsoF colonize tomato roots, produce AHL in the rhizosphere and increase systemic resistance of tomato plants against the fungal leaf pathogen, Alternaria alternata. The AHL-negative mutant S. liquefaciens MG44 was less effective in reducing symptoms and A. alternata growth as compared to the wild type. Salicylic acid (SA) levels were increased in leaves when AHL-producing bacteria colonized the rhizosphere. No effects were observed when isogenic AHL-negative mutant derivatives were used in these experiments. Furthermore, macroarray and Northern blot analysis revealed that AHL molecules systemically induce SA- and ethylene-dependent defence genes (i.e. PR1a, 26 kDa acidic and 30 kDa basic chitinase). Together, these data support the view that AHL molecules play a role in the biocontrol activity of rhizobacteria through the induction of systemic resistance to pathogens. 相似文献
1000.
Maras-Simunić M Grandić L Brnić D Simunić M Druzijanić N 《Collegium antropologicum》2008,32(1):311-313
In this study, a case of an ingested toothpick partially migrating from the sigmoid colon, causing massive lower gastrointestinal bleeding due to arterial-colic fistula, and stricture of the left ureter is presented. A 70-year-old male was admitted to the emergency department after having feces mixed with fresh and coagulated blood for the past two days. Computed tomography and retrograde ureteropyelography showed the stricture of the left ureter, 1.5 cm below the branching of iliac artery, without any signs of malignancy. Colonoscopy showed fresh blood in the rectum and sigmoid colon up to the neoplasm like granulation tissue mixed with fresh and coagulated blood, which almost obstructed the lumen. Explorative laparotomy showed a foreign body (toothpick) perforating the sigmoid colon through the mesenterial wall, and being stocked with one-third into the left internal iliac artery, causing arterial-colic fistula. The remaining part of the toothpick was surrounded by granulation tissue and chronic inflammatory process, pressing on the distal third of the left ureter. We conclude that a swallowed toothpick may cause a significant gastrointestinal injury with a wide variety of clinical manifestations, and it must be treated with caution. The imaging studies are often inadequate in detecting toothpicks, and thus, we insist on a physical examination, as the best indicator of injury. 相似文献