Universitätspublikationen
Refine
Year of publication
- 2005 (215) (remove)
Document Type
- Article (86)
- Part of Periodical (63)
- Review (17)
- Doctoral Thesis (15)
- Book (14)
- Preprint (6)
- Conference Proceeding (5)
- Report (3)
- Working Paper (2)
- Part of a Book (1)
Has Fulltext
- yes (215) (remove)
Is part of the Bibliography
- no (215)
Keywords
- Forschung (4)
- Frankfurt <Main> / Universität (4)
- Zeitschrift (4)
- Adorno (2)
- Asymmetrische Information (2)
- Irak (2)
- Malerei (2)
- Moral Hazard (2)
- Privatisierung des Krieges (2)
- Risikokapital (2)
Institute
- Medizin (29)
- E-Finance Lab e.V. (25)
- Präsidium (23)
- Rechtswissenschaft (22)
- Gesellschaftswissenschaften (19)
- Physik (15)
- Philosophie (12)
- Biochemie und Chemie (11)
- Institut für Sozialforschung (IFS) (10)
- Institut für Wirtschaft, Arbeit, und Kultur (IWAK) (9)
Cathepsin D (CatD) is a lysosomal aspartic proteinase and plays an important role in the degradation of proteins and in apoptotic processes induced by oxidative stress, cytokines, and aging. All of these stimuli are potent inducers of endothelial cell apoptosis. Therefore, we investigated the role of CatD in endothelial cell apoptosis and determined the underlying mechanisms. Incubation with 100-500 microm H2O2 for 12 h induced apoptosis in endothelial cells. To determine a role for CatD, we co-incubated endothelial cells with the CatD inhibitor pepstatin A. Pepstatin A as well as genetic knock down of CatD abolished H2O2-induced apoptosis. In contrast, overexpression of CatD wild type but not a catalytically inactive mutant of CatD (CatDD295N) induced apoptosis under basal conditions. To gain insights into the underlying mechanisms, we investigated the effect of CatD on reactive oxygen species (ROS) formation. Indeed, knocking down CatD expression reduced H2O2-induced ROS formation and apoptosis. The major redox regulator in endothelial cells is thioredoxin-1 (Trx), which plays a crucial role in apoptosis inhibition. Thus, we hypothesized that CatD may alter Trx protein levels and thereby promote formation of ROS and apoptosis. Incubation with 100 microm H2O2 for 6 h decreased Trx protein levels, whereas Trx mRNA was not altered. H2O2-induced Trx degradation was inhibited by pepstatin A and genetic knock down of CatD but not by other protease inhibitors. Incubation of unstimulated cell lysates with recombinant CatD significantly reduced Trx protein levels in vitro, which was completely blocked by pepstatin A pre-incubation. Overexpression of CatD reduced Trx protein in cells. Moreover, H2O2 incubation led to a translocation of Trx to the lysosomes prior to the induction of apoptosis. Taken together, CatD induces apoptosis via degradation of Trx protein, which is an essential anti-apoptotic and reactive oxygen species scavenging protein in endothelial cells.
Human endothelial circulating progenitor cells (CPCs) can differentiate to cardiomyogenic cells during co-culture with neonatal rat cardiomyocytes. Wnt proteins induce myogenic specification and cardiac myogenesis. Here, we elucidated the effect of Wnts on differentiation of CPCs to cardiomyogenic cells. CPCs from peripheral blood mononuclear cells were isolated from healthy volunteers and co-cultured with neonatal rat cardiomyocytes. 6–10 days after co-culture, cardiac differentiation was determined by α-sarcomeric actinin staining of human lymphocyte antigen-positive cells (fluorescence-activated cell-sorting analysis) and mRNA expression of human myosin heavy chain and atrial natriuretic peptide. Supplementation of co-cultures with Wnt11-conditioned medium significantly enhanced the differentiation of CPCs to cardiomyocytes (1.7 ± 0.3-fold), whereas Wnt3A-conditioned medium showed no effect. Cell fusion was not affected by Wnt11-conditioned medium. Because Wnts inhibit glycogen synthase kinase-3β, we further determined whether the glycogen synthase kinase-3β inhibitor LiCl also enhanced cardiac differentiation of CPCs. However, LiCl (10 mm) did not affect CPC differentiation. In contrast, Wnt11-conditioned medium time-dependently activated protein kinase C (PKC). Moreover, the PKC inhibitors bisindolylmaleimide I and III significantly blocked differentiation of CPCs to cardiomyocytes. PKC activation by phorbol 12-myristate 13-acetate significantly increased CPC differentiation to a similar extent as compared with Wnt11-conditioned medium. Our data demonstrate that Wnt11, but not Wnt3A, augments cardiomyogenic differentiation of human CPCs. Wnt11 promotes cardiac differentiation via the non-canonical PKC-dependent signaling pathway.
Within the ADD-model, we elaborate an idea by Vacavant and Hinchliffe [J. Phys. G 27 (2001) 1839] and show quantitatively how to determine the fundamental scale of TeV-gravity and the number of compactified extra dimensions from data at LHC. We demonstrate that the ADD-model leads to strong correlations between the missing ET in gravitons at different center of mass energies. This correlation puts strong constraints on this model for extra dimensions, if probed at s=5.5 TeV and s=14 TeV at LHC.
The kaon nuclear optical potential is studied including the effect of the Θ+ pentaquark. The one-nucleon contribution is obtained using an extension of the Jülich meson-exchange potential as bare kaon–nucleon interaction. Significant differences between a fully self-consistent calculation and the usually employed low-density Tρ approach are observed. The influence of the one-nucleon absorption process, KN→Θ+, on the kaon optical potential is negligible due to the small width of the pentaquark. In contrast, the two-nucleon mechanism, KNN→Θ+N, estimated from the coupling of the pentaquark to a two-meson cloud, provides the required amount of additional kaon absorption to reconcile with data the systematically low K+-nucleus reaction cross sections found by the theoretical models.
We solve the coupled Wong Yang–Mills equations for both U(1) and SU(2) gauge groups and anisotropic particle momentum distributions numerically on a lattice. For weak fields with initial energy density much smaller than that of the particles we confirm the existence of plasma instabilities and of exponential growth of the fields which has been discussed previously. Also, the SU(2) case is qualitatively similar to U(1), and we do find significant “abelianization” of the non-Abelian fields during the period of exponential growth. However, the effect nearly disappears when the fields are strong. This is because of the very rapid isotropization of the particle momenta by deflection in a strong field on time scales comparable to that for the development of Yang–Mills instabilities. This mechanism for isotropization may lead to smaller entropy increase than collisions and multiplication of hard gluons, which is interesting for the phenomenology of high-energy heavy-ion collisions.
Large extra dimensions could lower the Planck scale to experimentally accessible values. Not only is the Planck scale the energy scale at which effects of modified gravity become important. The Planck length also acts as a minimal length in nature, providing a natural ultraviolet cutoff and a limit to the possible resolution of spacetime.
In this Letter we examine the influence of the minimal length on the Casimir energy between two plates.
Alternative NADH dehydrogenases (NADH:ubiquinone oxidoreductases) are single subunit respiratory chain enzymes found in plant and fungal mitochondria and in many bacteria. It is unclear how these peripheral membrane proteins interact with their hydrophobic substrate ubiquinone. Known inhibitors of alternative NADH dehydrogenases bind with rather low affinities. We have identified 1-hydroxy-2-dodecyl-4(1H)quinolone as a high affinity inhibitor of alternative NADH dehydrogenase from Yarrowia lipolytica. Using this compound, we have analyzed the bisubstrate and inhibition kinetics for NADH and decylubiquinone. We found that the kinetics of alternative NADH dehydrogenase follow a ping-pong mechanism. This suggests that NADH and the ubiquinone headgroup interact with the same binding pocket in an alternating fashion.
Generation of reactive oxygen species (ROS) is increasingly recognized as an important cellular process involved in numerous physiological and pathophysiological processes. Complex I (NADH:ubiquinone oxidoreductase) is considered as one of the major sources of ROS within mitochondria. Yet, the exact site and mechanism of superoxide production by this large membrane-bound multiprotein complex has remained controversial. Here we show that isolated complex I from Yarrowia lipolytica forms superoxide at a rate of 0.15% of the rate measured for catalytic turnover. Superoxide production is not inhibited by ubiquinone analogous inhibitors. Because mutant complex I lacking a detectable iron-sulfur cluster N2 exhibited the same rate of ROS production, this terminal redox center could be excluded as a source of electrons. From the effect of different ubiquinone derivatives and pH on this side reaction of complex I we concluded that oxygen accepts electrons from FMNH or FMN semiquinone either directly or via more hydrophilic ubiquinone derivatives.
The transporter associated with antigen processing (TAP)-like (TAPL, ABCB9) belongs to the ATP-binding cassette transporter family, which translocates a vast variety of solutes across membranes. The function of this half-size transporter has not yet been determined. Here, we show that TAPL forms a homodimeric complex, which translocates peptides across the membrane. Peptide transport strictly requires ATP hydrolysis. The transport follows Michaelis-Menten kinetics with low affinity and high capacity. Different nucleotides bind and energize the transport with a slight predilection for purine bases. The peptide specificity is very broad, ranging from 6-mer up to at least 59-mer peptides with a preference for 23-mers. Peptides are recognized via their backbone, including the free N and C termini as well as side chain interactions. Although related to TAP, TAPL is unique as far as its interaction partners, transport properties, and substrate specificities are concerned, thus excluding that TAPL is part of the peptide-loading complex in the classic route of antigen processing via major histocompatibility complex class I molecules.