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81.
Traweger A Fuchs R Krizbai IA Weiger TM Bauer HC Bauer H 《The Journal of biological chemistry》2003,278(4):2692-2700
Zonula occludens proteins (ZOPs), currently comprising ZO-1, ZO-2, and ZO-3, belong to the family of membrane-associated guanylate kinase homologue (MAGUK) proteins that are involved in the organization of epithelial and endothelial intercellular junctions. ZOPs bind to the cytoplasmic C termini of junctional transmembrane proteins linking them to the actin cytoskeleton. They are characterized by several conserved modules, including three PDZ domains, one SH3 domain, and a guanylate kinase-like domain, elements indicating that ZOPs may serve multiple purposes. Interestingly, ZOPs contain some unique motifs not shared by other MAGUK family members, including nuclear localization and nuclear export signals and a leucine zipper-like sequence. Their potential involvement in cell growth and proliferation has been suggested earlier based on the observation that the N-terminal half of ZOPs displays significant similarity to the product of the Drosophila tumor suppressor gene lethal(1)discs-large (dlg). The nuclear targeting of ZOPs in subconfluent epithelial cell cultures is well documented, although the action of the junctional MAGUKs in the nucleus has remained elusive. Here we show for the first time that nuclear ZO-2 directly interacts with the DNA-binding protein scaffold attachment factor-B (SAF-B). Our results from two-hybrid assays and in vivo co-immunoprecipitation studies provide evidence to suggest that ZO-2 associates with the C-terminal portion of SAF-B via its PDZ-1 domain. We further demonstrate that enhanced green fluorescent protein (EGFP)- and DsRed-tagged ZO-2 and SAF-B fusion proteins partially co-localize in nuclei of transfected epithelial cells. As shown by laser confocal microscopy and epifluorescent analysis, nuclear ZO-2 is present in epithelial and endothelial cells, particularly in response to environmental stress conditions. Interestingly, no association of SAF-B with ZO-1 was found, which supports the notion that junctional MAGUKs serve nonredundant functions. 相似文献
82.
The amygdala modulates memory consolidation and the storage of emotionally relevant information in other brain areas, and itself comprises a site of neural plasticity during aversive learning. These processes have been intensively studied in Pavlovian fear conditioning, a leading aversive learning paradigm that is dependent on the structural and functional integrity of the amygdala. The rapidness and persistence, and the relative ease, with which this conditioning paradigm can be applied to a great variety of species have made it an attractive model for neurochemical and electrophysiological investigations on memory formation. In this review we summarise recent studies which have begun to unravel cellular processes in the amygdala that are critical for the formation of long-term fear memory and have identified molecular factors and mechanisms of neural plasticity in this brain area. 相似文献
83.
Decreased plasma and cerebrospinal fluid ascorbate levels in patients with septic encephalopathy 总被引:2,自引:0,他引:2
Voigt K Kontush A Stuerenburg HJ Muench-Harrach D Hansen HC Kunze K 《Free radical research》2002,36(7):735-739
Septic encephalopathies rapidly affect brain function without the involvement of a specific area causing a broad range of reversible neurologic symptoms. Capillary leakage including dysfunction of the blood-brain barrier has been proposed as a potential pathogenic mechanism in this entity. We tested the hypothesis that oxidative stress measured in plasma and cerebrospinal fluid (CSF) of patients suffering from septic encephalopathy could be linked to the neurologic symptoms of the disease. The neurologic symptoms of eleven patients with septic encephalopathy were described semiquantitatively through a score system. The ascorbate levels were significantly lower in both plasma and CSF from patients with septic encephalopathy than controls, and in CSF but not plasma this decrease correlated with the severity of neurologic symptoms. No significant changes were found for alpha-tocopherol. Our findings suggest that the short-term oxidative stress may be an important factor in the development of septic encephalopathy, possibly through dysregulation of the blood-brain barrier. 相似文献
84.
Sakaguchi T Gu X Golden HM Suh E Rhoads DB Reinecker HC 《The Journal of biological chemistry》2002,277(24):21361-21370
85.
The sugar code: functional lectinomics 总被引:16,自引:0,他引:16
Analysis of the genome and proteome assumes the focus of attention in efforts to relate biochemical coding with cell functionality. Among other chores in energy metabolism, the talents of carbohydrates to establish a high-density coding system give reason for a paradigmatic shift. The sequence complexity of glycans and glycan-processing enzymes (glycosyltransferases, glycosidases and enzymes introducing substituents such as sulfotransferases), the growing evidence for the importance of glycans from transgenic and knock-out animal models and the correlation of defects in glycosylation with diseases are substantial assets to portray oligosaccharides as code words in their own right. Matching the pace of progress in the work on glycoconjugates, the increasing level of refinement of our knowledge about lectins (definition of this term: carbohydrate-binding proteins, excluding sugar-specific antibodies, receptors of free mono- or disaccharides for transport or chemotaxis and enzymes modifying the bound carbohydrate) epitomizes the sphere of action of the sugar code (functional lectinomics). It encompasses, among other activities, intra- and intercellular transport processes, sensor branches of innate immunity, regulation of cell-cell (matrix) adhesion or migration and positive/negative growth control with implications for differentiation and malignancy. The Q & A approach taken in this review lists a series of arguments in a stepwise manner to make the reader wonder why it is only a rather recent process that the concept of the sugar code has taken root in deciphering the mechanistic versatility of biological information storage and transfer. 相似文献
86.
Alberto Sánchez-Guijo Vinzenz Oji Michaela F. Hartmann Hans-Christian Schuppe Heiko Traupe Stefan A. Wudy 《Journal of lipid research》2015,56(2):403-412
Steroid sulfatase (STS) deficiency is the underlying cause of the skin condition known as recessive X-linked ichthyosis (RXLI). RXLI patients show scales on their skin caused by high concentrations of cholesterol sulfate (CS), as they are not capable of releasing the sulfate group from its structure to obtain free cholesterol. CS has been reported, so far, as the sole sulfated steroid with increased concentrations in the blood of RXLI patients. A non-targeted LC-MS approach in negative mode detection (LC-MS precursor ion scan mode) was applied to serum samples of 12 RXLI patients and 19 healthy males. We found that CS was not the only sulfated compound consistently elevated in RXLI patients, because a group of compounds with a m/z of 481 was found in high concentrations too. Further LC-MS/MS demonstrated that the main contributor to the m/z 481 signal in RXLI serum is 27-hydroxycholesterol-3-sulfate (27OHC3S). Accordingly, a new method for 27OHC3S quantification in the context of RXLI has been developed and validated. Other hydroxycholesterol sulfate compounds were elevated as well in RXLI patients. 相似文献
87.
Marta Krystyna Kosinska Taryn E. Ludwig Gerhard Liebisch Ruiyan Zhang Hans-Christian Siebert Jochen Wilhelm Ulrich Kaesser Reinhard B. Dettmeyer Heiko Klein Bernd Ishaque Markus Rickert Gerd Schmitz Tannin A. Schmidt Juergen Steinmeyer 《PloS one》2015,10(5)
Background
Hyaluronic acid (HA), lubricin, and phospholipid species (PLs) contribute independently or together to the boundary lubrication of articular joints that is provided by synovial fluid (SF). Our study is the first reporting quantitative data about the molecular weight (MW) forms of HA, lubricin, and PLs in SF from cohorts of healthy donors, patients with early (eOA)- or late (lOA)-stage osteoarthritis (OA), and patients with active rheumatoid arthritis (RA).Methods
We used human SF from unaffected controls, eOA, lOA, and RA. HA and lubricin levels were measured by enzyme-linked immunosorbent assay. PLs was quantified by electrospray ionization tandem mass spectrometry. Fatty acids (FAs) were analyzed by gas chromatography, coupled with mass spectrometry. The MW distribution of HA was determined by agarose gel electrophoresis.Results
Compared with control SF, the concentrations of HA and lubricin were lower in OA and RA SF, whereas those of PLs were higher in OA and RA SF. Moreover, the MW distribution of HA shifted toward the lower ranges in OA and RA SF. We noted distinct alterations between cohorts in the relative distribution of PLs and the degree of FA saturation and chain lengths of FAs.Conclusions
The levels, composition, and MW distribution of all currently known lubricants in SF—HA, lubricin, PLs—vary with joint disease and stage of OA. Our study is the first delivering a comprehensive view about all joint lubricants during health and widespread joint diseases. Thus, we provide the framework to develop new optimal compounded lubricants to reduce joint destruction. 相似文献88.
89.
Hans-Christian Siebert Monika Burg-Roderfeld Thomas Eckert Sabine St?tzel Ulrike Kirch Tammo Diercks Martin J. Humphries Martin Frank Rainer Wechselberger Emad Tajkhorshid Steffen Oesser 《蛋白质与细胞》2010,1(4):393
We here present a detailed study of the ligand-receptor interactions between single and triple-helical strands of collagen and the α2A domain of integrin (α2A), providing valuable new insights into the mechanisms and dynamics of collagen-integrin binding at a sub-molecular level. The occurrence of single and triple-helical strands of the collagen fragments was scrutinized with atom force microscopy (AFM) techniques. Strong interactions of the triple-stranded fragments comparable to those of collagen can only be detected for the 42mer triple-helical collagen-like peptide under study (which contains 42 amino acid residues per strand) by solid phase assays as well as by surface plasmon resonance (SPR) measurements. However, changes in NMR signals during titration and characteristic saturation transfer difference (STD) NMR signals are also detectable when α2A is added to a solution of the 21mer single-stranded collagen fragment. Molecular dynamics (MD) simulations employing different sets of force field parameters were applied to study the interaction between triple-helical or single-stranded collagen fragments with α2A. It is remarkable that even single-stranded collagen fragments can form various complexes with α2A showing significant differences in the complex stability with identical ligands. The results of MD simulations are in agreement with the signal alterations in our NMR experiments, which are indicative of the formation of weak complexes between single-stranded collagen and α2A in solution. These results provide useful information concerning possible interactions of α2A with small collagen fragments that are of relevance to the design of novel therapeutic A-domain inhibitors. 相似文献
90.
Hans-Christian Siebert Sabine Andre Gerd Reuter Robert Kaptein Johannes F.G. Vliegenthart Hans-Joachim Gabius 《Glycoconjugate journal》1997,14(8):945-949
The human pentraxin serum amyloid P component (SAP) exhibits no microheterogeneity in its complex di-antennary glycan. To
elucidate whether the removal of sialic acids from this glycoprotein might affect the accessibility of certain amino acid
residues of the protein we employed the laser photo CIDNP approach as a sensitive tool. The CIDNP effect is generated by the
interaction of a photoexcited dye with reactive amino acids and results in enhanced absorption- or emission-signals which
can be observed for the three aromatic amino acids histidine, tryptophan, and tyrosine if they are accessible to the dye.
Therefore, this technique can be applied to explore surface exposure of these amino acid residues. The respective spectra
of SAP and enzymatically desialylated SAP were determined. Six tryptophan/histidine signals and one tyrosine signal are present
in the aromatic part of the CIDNP difference spectrum of SAP. The corresponding spectrum of desialylated SAP shows remarkable
alterations. The chemical shift of one Trp/His-characteristic signal is decreased by 0.1 ppm. One Trp/His-signal disappeared
and a new one was formed in the CIDNP difference spectrum of desialylated SAP, while the other signals were unaffected. The
Tyr signal has a clearly enhanced intensity in desialylated SAP. Therefore, the removal of sialic acid moieties from the single
N-glycan of each monomer apparently affects surface presentation of distinct CIDNP-reactive amino acids of SAP [1]. A conformational
change of the protein part of SAP in relation with a different orientation of the desialylated oligosaccharide chain in comparison
to the complete one is a possible explanation of our CIDNP results.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献