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Despite success with BRAFV600E inhibitors, therapeutic responses in patients with metastatic melanoma are short-lived because of the acquisition of drug resistance. We identified a mechanism of intrinsic multidrug resistance based on the survival of a tumor cell subpopulation. Treatment with various drugs, including cisplatin and vemurafenib, uniformly(More)
We employed confocal laser-scanning microscopy to monitor cholecystokinin (CCK)-evoked Ca(2+) signals in fluo-3-loaded mouse pancreatic acinar cells. CCK-8-induced Ca(2+) signals start at the luminal cell pole and subsequently spread toward the basolateral membrane. Ca(2+) waves elicited by stimulation of high-affinity CCK receptors (h.a.CCK-R) with 20 pM(More)
Adenosine triphosphate (ATP) dependent potassium channels (KATP channels) in heart ventricular muscle cells can be activated by depletion of intracellular ATP stores as well as by channel openers. In the present study we examined whether properties of KATP channels are dependent on the mode of activation. Whole-cell and single-channel currents were(More)
UNLABELLED Carotenoids are C-40 tetraterpenoid compounds with potential health beneficial effects. Major dietary sources include a variety of fruits and vegetables. Rapid screening methods are therefore desired, but their accuracy varies depending on the carotenoid profile and the matrix of the plant food. In the present study, 3 different methods were(More)
Receptor-mediated Ca2+ release from inositol (1,4,5)-trisphosphate (IP3)-sensitive Ca2+ stores causes "capacitative calcium entry" in many cell types (Putney, J. W., Jr. (1986) Cell Calcium 7, 1-12; Putney, J. W., Jr. (1990) Cell Calcium 11, 611-624). We used patch-clamp and fluorescence techniques in isolated mouse pancreatic acinar cells to identify ion(More)
Co-translational transport of polypeptides into the endoplasmic reticulum (ER) involves the Sec61 channel and additional components such as the ER lumenal Hsp70 BiP and its membrane-resident co-chaperone Sec63p in yeast. We investigated whether silencing the SEC61A1 gene in human cells affects co- and post-translational transport of presecretory proteins(More)
Sven Lang, Julia Benedix, Sorin V. Fedeles, Stefan Schorr, Claudia Schirra, Nico Schäuble, Carolin Jalal, Markus Greiner, Sarah Haßdenteufel, Jörg Tatzelt, Birgit Kreutzer, Ludwig Edelmann, Elmar Krause, Jens Rettig, Stefan Somlo, Richard Zimmermann* and Johanna Dudek Medical Biochemistry and Molecular Biology, Saarland University D-66421, Homburg, Germany(More)
Mammalian homologues of the Drosophila trp/trpl-gene-family code for "Ca(2+)-store-operated" channels. Here we describe the cloning and expression of a trp/trpl homologous gene from rat brain. The clone is named Rtrp3 because of its high homology to the recently described Htrp3 (Zhu et al (1996) Cell 85:661-671). Expression of Rtrp3 in the mammalian COS-1(More)
In order to fuse lytic granules (LGs) with the plasma membrane at the immunological synapse, cytotoxic T lymphocytes (CTLs) have to render these LGs fusion-competent through the priming process. In secretory tissues such as brain and neuroendocrine glands, this process is mediated by members of the Munc13 protein family. In human CTLs, mutations in the(More)
Cyclic ADP-ribose, a metabolite of NAD+ evokes Ca2+ release from intracellular stores in different cells. We have determined the activity of cADPr-producing enzymes (ADP-ribosyl cyclases) in different cellular fractions prepared from isolated pancreatic acinar cells by measuring the conversion of the beta-NAD+ analogs 1,N6-etheno-NAD and nicotinamide(More)