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81.
82.
Srikanth Perike Nurdan Özkucur Priyanka Sharma Wolfgang Staroske Robert Bläsche Kathrin Barth Richard HW Funk 《Experimental cell research》2014
The Na(+)/H(+) exchanger NHE3 colocalizes with beta-actin at the leading edge of directionally migrating cells. Using human osteosarcoma cells (SaOS-2), rat osteoblasts (calvaria), and human embryonic kidney (HEK) cells, we identified a novel role for NHE3 via beta-actin in anode and cathode directed motility, during electrotaxis. NHE3 knockdown by RNAi revealed that NHE3 expression is required to achieve constant directionality and polarity in migrating cells. Phosphorylated NHE3 (pNHE3) and beta-actin complex formation was impaired by the NHE3 inhibitor S3226 (IC50 0.02 µM). Fluorescence cross-correlation spectroscopy (FCCS) revealed that the molecular interactions between NHE3 and beta-actin in membrane protrusions increased 1.7-fold in the presence of a directional cue and decreased 3.3-fold in the presence of cytochalasin D. Data from flow cytometric analysis showed that membrane potential of cells (Vmem) decreases in directionally migrating, NHE3-deficient osteoblasts and osteosarcoma cells whereas only Vmem of wild type osteoblasts is affected during directional migration. These findings suggest that pNHE3 has a mechanical function via beta-actin that is dependent on its physiological activity and Vmem. Furthermore, phosphatidylinositol 3,4,5-trisphosphate (PIP3) levels increase while PIP2 remains stable when cells have persistent directionality. Both PI3 kinase (PI3K) and Akt expression levels change proportionally to NHE3 levels. Interestingly, however, the content of pNHE3 level does not change when PI3K/Akt is inhibited. Therefore, we conclude that NHE3 can act as a direction sensor for cells and that NHE3 phosphorylation in persistent directional cell migration does not involve PI3K/Akt during electrotaxis. 相似文献
83.
Verena Leder Martina Lummer Kathrin Tegeler Fabian Humpert Martin Lewinski Mark Schüttpelz Dorothee Staiger 《Biochemical and biophysical research communications》2014
Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased Kd value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R49 that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding. 相似文献
84.
Tanja Goyarts Klaus-Peter Brüssow Hana Valenta Ute Tiemann Kathrin Jäger Sven Dänicke 《Mycotoxin Research》2010,26(2):119-131
Six pregnant sows of 180.6 ± 5.6 kg were fed either a Fusarium-contaminated (4.42 mg DON and 48.3 μg ZON per kg, DON per os, n = 3) or a control diet (0.15 mg DON and 5 μg ZON/kg) in the period of days 63 and 70 of gestation. On day 63 of gestation,
sows fed the control diet were implanted with an intraperitoneal osmotic minipump (delivery rate of 10 μL/h, for 7 days) containing
50 mg pure (98%) DON in 2 ml 50% DMSO (DON ip, n = 3). Frequent plasma samples were taken to estimate the kinetics after oral and ip DON exposure. The intended continuous
delivery of DON by the intraperitoneal minipump could not be shown, as there was a plasma peak (Cmax) of 4.2–6.4 ng DON/mL either immediately (sow IP-2+3) or 2.5 h (sow IP-1) after implantation of the pump followed by a one-exponential
decline with a mean half-time (t1/2) of 1.75–4.0 h and only negligible DON plasma concentrations after 12 h. Therefore, the DON ip exposure has to be regarded
as one single dose 1 week before termination of experiment. The DON per os sows showed a mean basis level (after achieving
a steady state) of DON plasma concentration of about 6–8 ng/mL, as also indicated by the plasma DON concentration at the termination
of the experiment. On day 70, caesarean section was carried out, the fetuses were killed immediately after birth, and samples
of plasma, urine, and bile were taken to analyze the concentration of DON and its metabolite de-epoxy-DON. At necropsy there
were no macroscopic lesions observed in any organ of either sows or piglets. Histopathological evaluation of sows liver and
spleen revealed no alterations. The proliferation rate of peripheral blood mononuclear cells (PBMC) with or without stimulation
was not affected by the kind of DON treatment. The exposure of pregnant sows at mid-gestation (days 63–70, period of organogenesis)
to a Fusarium toxin-contaminated diet (4.42 mg DON and 0.048 mg ZON per kg) or pure DON via intraperitoneal osmotic minipump did not cause
adverse effects on health, fertility, maintenance of pregnancy, and performance of sows and their fetuses. However, DON was
detected in fetus plasma, indicating that this toxin can pass the placental barrier and may cause changes in the proportion
of white blood cells (lower monocyte and neutrophil and higher lymphocyte proportion in DON per os fetuses). 相似文献
85.
86.
Kerstin Radtke Daniela Kieneke André Wolfstein Kathrin Michael Walter Steffen Tim Scholz Axel Karger Beate Sodeik 《PLoS pathogens》2010,6(7)
Many viruses depend on host microtubule motors to reach their destined intracellular location. Viral particles of neurotropic alphaherpesviruses such as herpes simplex virus 1 (HSV1) show bidirectional transport towards the cell center as well as the periphery, indicating that they utilize microtubule motors of opposing directionality. To understand the mechanisms of specific motor recruitment, it is necessary to characterize the molecular composition of such motile viral structures. We have generated HSV1 capsids with different surface features without impairing their overall architecture, and show that in a mammalian cell-free system the microtubule motors dynein and kinesin-1 and the dynein cofactor dynactin could interact directly with capsids independent of other host factors. The capsid composition and surface was analyzed with respect to 23 structural proteins that are potentially exposed to the cytosol during virus assembly or cell entry. Many of these proteins belong to the tegument, the hallmark of all herpesviruses located between the capsid and the viral envelope. Using immunoblots, quantitative mass spectrometry and quantitative immunoelectron microscopy, we show that capsids exposing inner tegument proteins such as pUS3, pUL36, pUL37, ICP0, pUL14, pUL16, and pUL21 recruited dynein, dynactin, kinesin-1 and kinesin-2. In contrast, neither untegumented capsids exposing VP5, VP26, pUL17 and pUL25 nor capsids covered by outer tegument proteins such as vhs, pUL11, ICP4, ICP34.5, VP11/12, VP13/14, VP16, VP22 or pUS11 bound microtubule motors. Our data suggest that HSV1 uses different structural features of the inner tegument to recruit dynein or kinesin-1. Individual capsids simultaneously accommodated motors of opposing directionality as well as several copies of the same motor. Thus, these associated motors either engage in a tug-of-war or their activities are coordinately regulated to achieve net transport either to the nucleus during cell entry or to cytoplasmic membranes for envelopment during assembly. 相似文献
87.
Kathrin Rychli Christoph Kaun Philipp J. Hohensinner Adrian J. Dorfner Stefan Pfaffenberger Alexander Niessner Michael Bauer Wolfgang Dietl Bruno K. Podesser Gerald Maurer Kurt Huber Johann Wojta 《Journal of cellular and molecular medicine》2010,14(1-2):198-205
Cardiac diseases such as myocardial infarction and heart failure are among the leading causes of death in western societies. Therapeutic angiogenesis has been suggested as a concept to combat these diseases. The biology of angiogenic factors expressed in the heart such as vascular endothelial growth factor (VEGF) is well studied, whereas data on anti-angiogenic mediators in the heart are scarce. Here we study the expression of the anti-angiogenic factor pigment epithelium-derived factor (PEDF) in the human heart and in human cardiac cells. PEDF expression could be detected in human cardiac tissue on the protein and mRNA levels. PEDF mRNA levels were significantly lower in explanted human ischemic hearts as compared to healthy hearts. Our in vitro experiments showed that human adult cardiac myocytes and fibroblasts constitutively secrete PEDF. In addition to anoxic conditions, cobalt chloride, 2,2'dipyridyl and dimethoxally glycine, which stabilize hypoxia inducible factor-α decreased PEDF expression. Furthermore we show that PEDF inhibits VEGF-induced sprouting. We have identified PEDF in healthy and ischemic human hearts and we show that PEDF expression is down-regulated by low oxygen levels. Therefore, we suggest a role for PEDF in the regulation of angiogenesis in the heart and propose PEDF as a possible therapeutic target in heart disease. 相似文献
88.
89.
90.
Mauricio Hunsche Kathrin Bürling Amina Sirag Saied Michaela Schmitz-Eiberger Muhammad Sohail Jens Gebauer Georg Noga Andreas Buerkert 《Plant Growth Regulation》2010,61(3):253-263
Seedlings of the salt-tolerant plant grewia [Grewia tenax (Forssk.) Fiori] and the moderately salt-tolerant tamarind (Tamarindus indica L.) were grown under controlled conditions and treated daily with NaCl solutions to investigate mechanisms of tolerance to
salinity. Leaf micromorphology, cuticular wax load, chlorophyll fluorescence and light remission, as well as antioxidative
potential were evaluated. As confirmed by energy-dispersive X-ray microanalysis in both species, absorption of sodium and
chlorine increased with rising NaCl concentration in the treatment solution. In parallel, accumulation of calcium in grewia
leaves was strongly reduced, leading to less crystals of calcium oxalate in leaf tissue. In grewia the cuticular wax load,
chlorophyll content, and electron transport rate (ETR) were significantly reduced by comparatively low NaCl concentrations.
In tamarind, in contrast, wax load and ETR were not significantly affected, while the decrease of chlorophyll content was
less pronounced. Measurements of the antioxidative capacity and the imbalance between values of lipophilic and hydrophilic
extracts at different NaCl concentrations confirmed that grewia is more salt tolerant than tamarind. This higher tolerance
degree seemed to be associated with grewias’ more efficient scavenging of free radicals and the regulation of the antioxidative
potential in lipophilic and hydrophilic extracts. 相似文献