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651.
Apoptotic pathways involved in U937 cells exposed to LDL oxidized by hypochlorous acid 总被引:3,自引:0,他引:3
Vicca S Massy ZA Hennequin C Rihane D Drüeke TB Lacour B 《Free radical biology & medicine》2003,35(6):603-615
Oxidized low-density lipoproteins (oxLDL) play a critical role in atherogenesis. One oxidative pathway of LDL involves myeloperoxidase, which catalyzes the production of hypochlorous acid (HOCl) in monocytes. We investigated the apoptotic mechanism induced by oxLDL, generated by HOCl treatment of native LDL, in human monocytic U937 cell line. The involvement of the mitochondrial apoptotic pathway was analyzed in Bcl-2-overexpressing clones, generated from U937 cells. HOCl-oxLDL induced in U937 cells (i) a marked caspase-dependent increase of apoptosis, (ii) a loss of mitochondrial membrane potential, (iii) a specific activation of caspase-2, -3, -8, and -9, and (iv) a similar degree of apoptosis in presence or absence of anti-Fas and anti-TNF-R1 antibodies. Moreover, the degree of HOCl-oxLDL-induced caspase-3 and -8 activation, and apoptosis was significantly reduced in U937/Bcl-2 cells, with no activation of caspase-9. By contrast, Cu-oxLDL-mediated apoptosis in U937 cells involved exclusively the mitochondrial pathway. In conclusion, the mechanism of HOCl-oxLDL-induced apoptosis in monocytic U937 cells involves the two pathways of apical caspase activation: (i) death receptor-mediated caspase-8 and (ii) mitochondria-mediated caspase-9. This converges in the activation of executing caspases, including caspase-3, and apoptosis. The interference of Bcl-2 overexpression with HOCl-oxLDL-induced apoptosis suggests the importance of mitochondrial involvement in this apoptotic mechanism. 相似文献
652.
Franziska U Wöhrle Roger J Daly Tilman Brummer 《Cell communication and signaling : CCS》2009,7(1):1-28
Since their discovery a little more than a decade ago, the docking proteins of the Gab/DOS family have emerged as important signalling elements in metazoans. Gab/DOS proteins integrate and amplify signals from a wide variety of sources including growth factor, cytokine and antigen receptors as well as cell adhesion molecules. They also contribute to signal diversification by channelling the information from activated receptors into signalling pathways with distinct biological functions. Recent approaches in protein biochemistry and systems biology have revealed that Gab proteins are subject to complex regulation by feed-forward and feedback phosphorylation events as well as protein-protein interactions. Thus, Gab/DOS docking proteins are at the centre of entire signalling subsystems and fulfil an important if not essential role in many physiological processes. Furthermore, aberrant signalling by Gab proteins has been increasingly linked to human diseases from various forms of neoplasia to Alzheimer's disease. In this review, we provide a detailed overview of the structure, effector functions, regulation and evolution of the Gab/DOS family. We also summarize recent findings implicating Gab proteins, in particular the Gab2 isoform, in leukaemia, solid tumours and other human diseases. 相似文献
653.
Lisa Ott Martina Höller Johannes Rheinlaender Tilman E Schäffer Michael Hensel Andreas Burkovski 《BMC microbiology》2010,10(1):257
Background
Corynebacterium diphtheriae, the causative agent of diphtheria, is well-investigated in respect to toxin production, while little is known about C. diphtheriae factors crucial for colonization of the host. In this study, we investigated strain-specific differences in adhesion, invasion and intracellular survival and analyzed formation of pili in different isolates. 相似文献654.
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Mauerhofer Lisa-Maria Reischl Barbara Schmider Tilman Schupp Benjamin Nagy Kinga Pappenreiter Patricia Zwirtmayr Sara Schuster Bernhard Bernacchi Sébastien Seifert Arne H. Paulik Christian Rittmann Simon K.-M. R. 《Applied microbiology and biotechnology》2018,102(17):7643-7656
Applied Microbiology and Biotechnology - Accumulation of carbon dioxide (CO2), associated with global temperature rise, and drastically decreasing fossil fuels necessitate the development... 相似文献
658.
Albert Busch Tilman Kiel Wolfgang-M. Heupel Stefan Hübner 《Experimental cell research》2009,315(14):2373-2385
Lamins, which form the nuclear lamina, not only constitute an important determinant of nuclear architecture, but additionally play essential roles in many nuclear functions. Mutations in A-type lamins cause a wide range of human genetic disorders (laminopathies). The importance of lamin A (LaA) in the spatial arrangement of nuclear pore complexes (NPCs) prompted us to study the role of LaA mutants in nuclear protein transport. Two mutants, causing prenatal skin disease restrictive dermopathy (RD) and the premature aging disease Hutchinson Gilford progeria syndrome, were used for expression in HeLa cells to investigate their impact on the subcellular localization of NPC-associated proteins and nuclear protein import. Furthermore, dynamics of the LaA mutants within the nuclear lamina were studied. We observed affected localization of NPC-associated proteins, diminished lamina dynamics for both LaA mutants and reduced nuclear import of representative cargo molecules. Intriguingly, both LaA mutants displayed similar effects on nuclear morphology and functions, despite their differences in disease severity. Reduced nuclear protein import was also seen in RD fibroblasts and impaired lamina dynamics for the nucleoporin Nup153. Our data thus represent the first study of a direct link between LaA mutant expression and reduced nuclear protein import. 相似文献
659.
Rhythmic body contraction is a phenomenon in the Porifera, which is only partly understood. As a foundation for the understanding of the functional morphology of the highly contractile Tethya wilhelma, we performed a qualitative and quantitative volumetric 3D-analysis of the morphology of a complete non-contracted specimen at resolutions of 5.2 and 6.9 μm, using synchrotron radiation based X-ray computed microtomography (SR-μCT). For the first time, we were able to visualize all three major body structures of a complete poriferan without dissection of the shock-frozen, fixed and contrasted specimen in a near-to-life confirmation: poriferan tissue, mineral skeleton and aquiferous system. Applying a ‘virtual cast’ technique allowed us to analyze the structural details of the complete canal structure. Our results imply an extensive re-circulation of water inside the poriferan due to well-developed by-pass-canals, connecting excurrent and incurrent system. Nevertheless, the oscule region is strictly separated from the incurrent system. Based on our data, we developed a hypothetical flow regime for T. wilhelma, which explains the necessity of by-pass canals to minimize pressure boosts in the canal system during contraction. Additionally, re-circulation optimizes nutrient uptake, within small-sized poriferans, like T. wilhelma. Quantitative analysis allowed us to measure volumes and surfaces, displaying remarkable organizational differences between choanosome and cortex, by means of distribution of morphological elements. The surface-to-volume ratio proved to be very high, underlining the importance of the poriferan pinacoderm. We support a pinacoderm-contraction hypothesis.Electronic Supplementary Material Supplementary material is available to authorised users in the online version of this article at .Dedicated to Prof. Dr. Michele Sarà (Genova, Italy), in honour of his 80th birthday in 2006. 相似文献
660.
The present status of erythrocyte spectrin structure: the 106-residue repetitive structure is a basic feature of an entire class of proteins 总被引:10,自引:0,他引:10
D W Speicher 《Journal of cellular biochemistry》1986,30(3):245-258
Spectrin, the major component of the erythroid membrane skeleton, is a long, asymmetrical rodlike protein that interacts with several other proteins to form a two-dimensional membrane skeleton. Progress in several laboratories over the past few years including substantial partial peptide and nucleotide sequence determination has greatly enhanced our knowledge of the structural properties of this large molecule (heterodimer = 465,000 daltons). The alpha and beta subunits are homologous with approximately 30% identity. They are aligned in an antiparallel side-to-side orientation with the amino- and carboxy-termini near opposite physical ends of the molecule. The predominant structural feature elucidated from sequencing this large molecule is the nearly universal occurrence in both subunits of a single type of repetitive structure. The periodicity of this homologous structure is exactly 106 amino acid residues. As many as 36 homologous, but nonidentical, repeats exist and comprise more than 90% of the mass of the heterodimer. Each of these repetitive units is folded into a triple-stranded structure that is highly helical. Peptide maps, antibody crossreactivity, peptide sequence analysis, and more recently nucleic acid sequences have defined several major properties of the erythroid molecule and related proteins in other tissues. Tissue-specific spectrins have the same 106-residue repetitive structure and show sequence homology to erythroid spectrin. 相似文献