A5049476793- Ion channel regulation and function
- Sphingolipid Metabolism and Signaling
- Signaling Pathways in Disease
- Carbohydrate Chemistry and Synthesis
- Cellular transport and secretion
- Lipid Membrane Structure and Behavior
- Peptidase Inhibition and Analysis
- Neuroscience and Neuropharmacology Research
- Chemical Synthesis and Analysis
- interferon and immune responses
- Protein Kinase Regulation and GTPase Signaling
- Pancreatic function and diabetes
- Advanced biosensing and bioanalysis techniques
- Receptor Mechanisms and Signaling
- Glycosylation and Glycoproteins Research
- PI3K/AKT/mTOR signaling in cancer
- Calcium signaling and nucleotide metabolism
- Cardiac electrophysiology and arrhythmias
- Endoplasmic Reticulum Stress and Disease
- Neuroinflammation and Neurodegeneration Mechanisms
- Viral Infectious Diseases and Gene Expression in Insects
- RNA and protein synthesis mechanisms
- Inflammasome and immune disorders
- Insect Resistance and Genetics
- Galectins and Cancer Biology
Novartis (Switzerland)
2013-2024
Novartis Institutes for BioMedical Research
2011-2024
Novartis (China)
2023
Novartis (Austria)
2006
École Polytechnique Fédérale de Lausanne
1992-2003
ETH Zurich
1987-2002
National Institutes of Health
1990-1996
National Cancer Institute
1989-1996
Russian Academy of Sciences
1995
Institute of Biochemistry
1995
BAF312 is a next-generation sphingosine 1-phosphate (S1P) receptor modulator, selective for S1P(1) and S1P(5 ) receptors. receptors are essential lymphocyte egress from lymph nodes drug target in immune-mediated diseases. Here, we have characterized the immunomodulatory potential of S1P receptor-mediated effects on heart rate using preclinical human data.BAF312 was tested rat experimental autoimmune encephalomyelitis (EAE) model. Electrophysiological recordings G-protein-coupled inwardly...
Tumor necrosis factor (TNF) is a key driver of several inflammatory diseases, such as rheumatoid arthritis, bowel disease, and psoriasis, in which affected tissues show an interferon-stimulated gene signature. Here, we demonstrate that TNF triggers type-I interferon response dependent on the cyclic guanosine monophosphate-AMP synthase (cGAS)-stimulator genes (STING) pathway. We inhibits PINK1-mediated mitophagy leads to altered mitochondrial function increase cytosolic mtDNA levels. Using...
Antibodies against the four isoforms of human plasma membrane Ca2+-ATPase (PMCA) were raised using an N-terminal sequence pump as epitope. The antibodies PMCA 1, 2, and 3 not species-specific, e.g. they also recognized corresponding proteins in rat, whereas that isoform 4 failed to do so.The tissue distribution was estimated by Western blot analysis. Two, PMCA1 PMCA4, expressed all tissues tested (with exception choroid plexus, where former detected). In most signal from protein exceeded...
Two types (I and II) of cDNAs encoding the large (A) subunit calcineurin, a calmodulin-regulated protein phosphatase, were isolated from human basal ganglia brainstem mRNA. The complete sequences two calcineurin clones are identical except for 54-base-pair insert in type I clone different 3' ends including part coding sequence C termini proteins. These findings suggest that A consists at least isozymes may result alternative splicing events. forms enzyme differ terminus, which contains an...
Highly purified tryptic peptides of calmodulin have been obtained by high-performance liquid chromatography.Tryptic cleavage in the presence Ca2+ results two main fragments which identified analysis amino acid composition as 1-77 and 78-148.In absence Ca2+, trypsin yields 1-106,l-90, 107-148.Only 78-148 1-106 are still able to stimulate Ca2+-ATPase erythrocytes, albeit much less efficiently on a molar basis, than intact calmodulin.On other hand, same were unable calmodulin-dependent cyclic...
In the central nervous system, release of Ca 2+ from intracellular stores contributes to numerous functions, including neurotransmitter and long-term potentiation depression. We have investigated developmental profile regulation inositol 1,4,5-trisphosphate receptor (IP3R) ryanodine (RyR) in primary cultures cerebellar granule cells. The expression both types increases during development. Whereas type 1 IP3R appears be regulated by influx through L channels or N -methyl- d -aspartate (NMDA)...
In vivo phosphorylation of FTY720 (1) in rats and humans resulted exclusively the biologically active (S)-configured enantiomer, which was proven by an ex o-phthaldialdehyde derivatization protocol especially elaborated for phosphates 1. Starting from prochiral amino alcohol 1, racemic enantiomerically pure 1 were synthesized. Pure enantiomers obtained after purification a partially protected key intermediate on enantioselective support. The absolute stereochemistry determined X-ray diffraction.
Abstract Sphingosine‐1‐phosphate (S1P) receptors are widely expressed in the central nervous system where they thought to regulate glia cell function. The phosphorylated version of fingolimod/FTY720 (FTY720P) is active on a broad spectrum S1P and parent compound currently phase III clinical trials for treatment multiple sclerosis. Here, we aimed identify which type(s) receptor(s) targeted by FTY720P. Using calcium imaging mixed cultures from embryonic rat cortex show that astrocytes major...
Full-length cDNAs for the three human plasma membrane Ca2+ pump isoforms 2 (PMCA2) differently spliced at A site were constructed and transferred to baculovirus. The corresponding proteins expressed after infection in Sf9 insect cells. high levels retained canonical properties of pump. alternative splicing process failed produce functional differences detectable with methods used. Ca(2+)-dependent ATPase activity PMCA2 pumps had a 5-10-fold higher affinity calmodulin than PMCA4 same system....
Plasma membrane Ca2+ ATPase (PMCA) pump isoforms 2, 3, and 1CII are expressed in large amounts the cerebellum of adult rats but only minimally neonatal cerebellum. These were almost undetectable rat cerebellar granule cells 1–3 days after plating, they became highly 7–9 culturing under depolarizing conditions (25 mm KCl). The behavior isoform 4 was different: it clearly detectable down-regulated by cultured cells. 25 mmKCl-activated l-type channels, significantly increasing cytosolic Ca2+....
The four basic isoforms of the plasma membrane Ca2+ pump and two C-terminally truncated spliced variants PMCA4CII(4a) 3CII(3a) were transiently overexpressed in Chinese hamster ovary cells together with aequorin targeted to cytosol, endoplasmic reticulum, mitochondria. As PMCA3CII(3a) had not yet been cloned studied, it was for this study, partially purified, characterized. At variance corresponding variant PMCA4, which studied previously, very high calmodulin affinity. All influenced...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT3-(Trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine, a hydrophobic, photoreactive probe, labels calmodulin and fragments in calcium(2+)-dependent wayJoachim Krebs, Jacqueline Buerkler, Danilo Guerini, Josef Brunner, Ernesto CarafoliCite this: Biochemistry 1984, 23, 3, 400–403Publication Date (Print):January 31, 1984Publication History Published online1 May 2002Published inissue 31 January...
The molecular mechanism underlying the clinical efficacy of FTY720-P is thought to involve persistent internalization and enhanced degradation S1P1 receptor subtype (S1P1R). We have investigated whether binding kinetics β-arrestin recruitment could play a role in S1P1R by FTY720-P.[(3) H]-FTY720-P [(33) P]-S1P were used label CHO-S1P1/3Rs for studies. Ligand was assessed through [(35) S]-GTPγS recruitment. Metabolic stability evaluated using bioassay measuring intracellular Ca(2+) release....