GRAPES FOR AMYLOIDS: The red wine compound resveratrol can effectively inhibit the formation of IAPP amyloid that is found in type II diabetes. Our in vitro inhibition results do not depend on the antioxidant activity of resveratrol. Further, the markedly enhanced cell survival in the presence of resveratrol also indicates that the small oligomeric structures that are observed during beta-sheet formation are not toxic and could be off-pathway assembly products.
The islet amyloid polypeptide (IAPP) or amylin is a pancreatic hormone and crucially involved in the pathogenesis of type-II diabetes mellitus (T2DM). Aggregation and amyloid formation of IAPP is considered as the primary culprit for pancreatic beta-cell loss in T2DM patients. In this study, first X-ray reflectivity (XRR) measurements on IAPP at lipid interfaces have been carried out, providing a molecular level characterization of the first steps of the lipid-induced fibrillation process of IAPP, which is initiated by lipid-induced nucleation, oligomerization, followed by detachment of larger IAPP aggregate structures from the lipid membrane, and terminated by the formation of mature fibrils in the bulk solution. The adsorption process of IAPP at lipid interfaces in the absence and presence of negatively charged lipid has also been studied by complementary ATR-FTIR spectroscopic measurements. The morphological properties were followed by atomic force microscopy (AFM). Moreover, we show that the polyphenolic red wine compound resveratrol is able to inhibit IAPP aggregation also in the presence of aggregation-fostering negatively charged lipid interfaces, revealing its potential as a drug candidate for T2DM.
Klein und zackig: Die pathologische Aggregation von Amylin (IAPP), die bei Diabetes mellitus Typ II auftritt, wird durch nanomolare Konzentrationen an niedermolekularen Inhibitoren auf Rhodaninbasis effektiv gehemmt. Diese Wirkung ließ sich rasterkraftmikroskopisch nachweisen (siehe AFM‐Bild).
Fluorescein permeable junctions occur infrequently between unsensitized C57BL/6 lymphocytes (H‐2b) and DBA/2 mastocytoma cells (H‐2d), but the incidence of such junctions increases significantly with lymphocytes from animals sensitized against the mastocytes. The mastocytoma cells were labeled intracellularly with fluorescein using permeant (non‐fluorescent) fluorescein dipropionate which is hydrolyzed to free fluorescein within the cells; they were additionally stained with neutral red.
As an in vitro model of cell‐mediated cytotoxicity the Brunner system was used in which close contact is a prerequisite of cell lysis. With contacts of aggressor cells to targets fluorescein permeable junctions were found in 17 out of 23 experiments, or 168 times, when sensitized spleen cells from female C57BL mice took part in the reaction. This incidence is significantly greater than in control experiments with normal spleen cells, when fluorescein permeable junctions were observed only 28 times and in only 9 out of 23 experiments.
A concept for the determination of concentrations in microchannels using FT-IR spectroscopy in transmission is presented. The fundamental idea of spatially resolved measurements along several measuring points was implemented in a single-channel microreactor. Compared to existing microreactor setups for the analysis of fast chemical reactions or mixing processes, the presented concept enables longer residence times at appropriate resolution. Once steady-state conditions were reached in the reactor, mid-infrared spectra were collected at different locations. Information throughout the considered conversion range is available, which is of great importance to analyze inhibitory effects, next to the kinetic constants (vmax and KM). Therefore, this technology enables a rapid screening of (bio-)catalysts, substrate specificity and process conditions. In particular, the analysis of real substrates instead of model substrates and the possibility to follow side reactions and follow-up reactions during enzymatic catalysis open a broad field of application.
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