8 research outputs found
Hemostatic factors occupy new territory: The role of the urokinase receptor system and kininogen in inflammation
The Marburg I polymorphism of factor VII activating protease is associated with low proteolytic and low pro-coagulant activity
Cardiolog
Radon and thoron inhalation doses in dwellings with earthen architecture: Comparison of measurement methods.
The radioactive noble gas radon (222Rn) and its decay products have been considered a health risk in the indoor environment for many years because of their contribution to the radiation dose of the lungs. The radioisotope thoron (220Rn) and its decay products came into focus of being a health risk only recently. The reason for this is its short half-life, so only building material can become a significant source for indoor thoron. In this study, dwellings with earthen architecture were investigated with different independent measurement techniques in order to determine appropriate methods for reliable dose assessment of the dwellers. While for radon dose assessment, radon gas measurement and the assumption of a common indoor equilibrium factor often are sufficient, thoron gas has proven to be an unreliable surrogate for a direct measurement of thoron decay products. Active/time-resolved but also passive/integrating measurements of the total concentration of thoron decay products demonstrated being precise and efficient methods for determining the exposure and inhalation dose from thoron and its decay products. Exhalation rate measurements are a useful method for a rough dose estimate only if the exhalation rate is homogeneous throughout the house. Before the construction of a building in-vitro exhalation rate measurements on the building material can yield information about the exposure that is to be expected. Determining the unattached fraction of radon decay products and even more of thoron decay products leads to only a slightly better precision; this confirms the relative unimportance of the unattached thoron decay products due to their low concentration. The results of this study thereby give advice on the proper measurement method in similar exposure situations
The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function
The F-box protein FBXW7 is the substrate-recruiting subunit of an SCF ubiquitin ligase and a major tumor-suppressor protein that is altered in several human malignancies. Loss of function of FBXW7 results in the stabilization of numerous proteins that orchestrate cell proliferation and survival. Little is known about proteins that directly regulate the function of this protein. In the current work, we have mapped the interactome of the enigmatic pseudophosphatase STYX We reasoned that a catalytically inactive phosphatase might have adopted novel mechanisms of action. The STYX interactome contained several F-box proteins, including FBXW7. We show that STYX binds to the F-box domain of FBXW7 and disables its recruitment into the SCF complex. Therefore, STYX acts as a direct inhibitor of FBXW7, affecting the cellular levels of its substrates. Furthermore, we find that levels of STYX and FBXW7 are anti-correlated in breast cancer patients, which affects disease prognosis. We propose the STYX-FBXW7 interaction as a promising drug target for future investigations
Proteolytic activation of the epithelial sodium channel (ENaC) by factor VII activating protease (FSAP) and its relevance for sodium retention in nephrotic mice.
Proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases is thought to contribute to renal sodium retention in nephrotic syndrome. However, the identity of the responsible proteases remains elusive. This study evaluated factor VII activating protease (FSAP) as a candidate in this context. We analyzed FSAP in the urine of patients with nephrotic syndrome and nephrotic mice and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in FSAP-deficient mice (Habp2-/-) with experimental nephrotic syndrome induced by doxorubicin. In urine samples from nephrotic humans, high concentrations of FSAP were detected both as zymogen and in its active state. Recombinant serine protease domain of FSAP stimulated ENaC-mediated whole-cell currents in a time- and concentration-dependent manner. Mutating the putative prostasin cleavage site in γ-ENaC (γRKRK178AAAA) prevented channel stimulation by the serine protease domain of FSAP. In a mouse model for nephrotic syndrome, active FSAP was present in nephrotic urine of Habp2+/+ but not of Habp2-/- mice. However, Habp2-/- mice were not protected from sodium retention compared to nephrotic Habp2+/+ mice. Western blot analysis revealed that in nephrotic Habp2-/- mice, proteolytic cleavage of α- and γ-ENaC was similar to that in nephrotic Habp2+/+ animals. In conclusion, active FSAP is excreted in the urine of nephrotic patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site of γ-ENaC. However, endogenous FSAP is not essential for sodium retention in nephrotic mice