A5034841737- Inflammatory mediators and NSAID effects
- Estrogen and related hormone effects
- Natural product bioactivities and synthesis
- Synthesis and biological activity
- Cancer, Lipids, and Metabolism
- Bioactive Compounds and Antitumor Agents
- Cholesterol and Lipid Metabolism
- Fatty Acid Research and Health
- Eicosanoids and Hypertension Pharmacology
- Lipid metabolism and biosynthesis
- NF-κB Signaling Pathways
- Sphingolipid Metabolism and Signaling
- Endoplasmic Reticulum Stress and Disease
- Natural Compound Pharmacology Studies
- Phytochemistry and Bioactive Compounds
- Pharmacological Effects of Medicinal Plants
- Free Radicals and Antioxidants
- Microbial Natural Products and Biosynthesis
- Autophagy in Disease and Therapy
- Synthesis of Organic Compounds
- Retinoids in leukemia and cellular processes
- Asthma and respiratory diseases
- Cannabis and Cannabinoid Research
- Ferroptosis and cancer prognosis
- Bone Metabolism and Diseases
Universität Innsbruck
2019-2025
Friedrich Schiller University Jena
2016-2025
University of Graz
2024-2025
Jena University Hospital
2015-2021
University of Tübingen
2008-2017
The University of Tokyo
2010-2017
Monash University
2017
Schiller International University
2013
Yancheng Institute of Technology
2012
Goethe University Frankfurt
2008
Abstract Therapy resistance and metastasis, the most fatal steps in cancer, are often triggered by a (partial) activation of epithelial–mesenchymal transition (EMT) programme. A mesenchymal phenotype predisposes to ferroptosis, cell death pathway exerted an iron oxygen-radical-mediated peroxidation phospholipids containing polyunsaturated fatty acids. We here show that various forms EMT activation, including TGFβ stimulation acquired therapy resistance, increase ferroptosis susceptibility...
The anti-inflammatory drug licofelone [=ML3000; 2-[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1<i>H</i>-pyrrolizin-5-yl] acetic acid], currently undergoing phase III trials for osteoarthritis, inhibits the prostaglandin (PG) and leukotriene biosynthetic pathway. Licofelone was reported to suppress formation of PGE<sub>2</sub> in various cell-based test systems, but underlying molecular mechanisms are not entirely clear. Here, we examined direct interference with enzymes...
Zileuton is the only 5-lipoxygenase (5-LOX) inhibitor marketed as a treatment for asthma, and often utilized selective tool to evaluate role of 5-LOX leukotrienes. The aim this study was investigate effect zileuton on prostaglandin (PG) production in vitro vivo.Peritoneal macrophages activated with lipopolysaccharide (LPS)/interferon γ (LPS/IFNγ), J774 human whole blood stimulated LPS were used models rat carrageenan-induced pleurisy an vivo model.Zileuton suppressed PG biosynthesis by...
Abstract Systemic vitamin E metabolites have been proposed as signaling molecules, but their physiological role is unknown. Here we show, by library screening of potential human metabolites, that long-chain ω-carboxylates are potent allosteric inhibitors 5-lipoxygenase, a key enzyme in the biosynthesis chemoattractant and vasoactive leukotrienes. 13-((2 R )-6-hydroxy-2,5,7,8-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoic acid (α-T-13′-COOH) can be synthesized from α-tocopherol...
Nonsteroidal anti-inflammatory drugs interfere with the metabolism of arachidonic acid to proinflammatory prostaglandins and leukotrienes by targeting cyclooxygenases (COXs), 5-lipoxygenase (LOX), or 5-LOX-activating protein (FLAP). These related enzymes act in conjunction marked crosstalk within a complex lipid mediator (LM) network where also specialized proresolving LMs (SPMs) are formed. Here, we present how prominent LM pathways can be differentially modulated human M1 M2 macrophage...
Abstract Cytotoxic stress activates stress-activated kinases, initiates adaptive mechanisms, including the unfolded protein response (UPR) and autophagy, induces programmed cell death. Fatty acid unsaturation, controlled by stearoyl-CoA desaturase (SCD)1, prevents cytotoxic but mechanisms are diffuse. Here, we show that 1,2-dioleoyl- sn -glycero-3-phospho-(1’-myo-inositol) [PI(18:1/18:1)] is a SCD1-derived signaling lipid, which inhibits p38 mitogen-activated kinase activation, counteracts...
Ribosome biogenesis is initiated by RNA polymerase I (Pol I)-mediated synthesis of pre-ribosomal (pre-rRNA). Pol activity was previously linked to longevity, but the underlying mechanisms were not studied beyond effects on nucleolar structure and protein translation. Here we use multi-omics functional tests show that curtailment remodels lipidome preserves mitochondrial function promote longevity in Caenorhabditis elegans. Reduced pre-rRNA improves energy homeostasis metabolic plasticity...
Frankincense, the gum resin derived from Boswellia species, showed anti-inflammatory efficacy in animal models and pilot clinical studies. Boswellic acids (BAs) are assumed to be responsible for these effects but their vivo molecular modes of action incompletely understood.A protein fishing approach using immobilized BA surface plasmon resonance (SPR) spectroscopy were used reveal microsomal prostaglandin E(2) synthase-1 (mPGES1) as a BA-interacting protein. Cell-free cell-based assays...
Abstract Prostaglandin E2 (PGE2) plays a crucial role in the apparent link between tumor growth and chronic inflammation. Cyclooxygenase (COX)-2 microsomal PGE2 synthase-1, which are overexpressed many cancers, functionally coupled thus produce massive various tumors. Curcumin, polyphenolic β-diketone from tumeric with anti-carcinogenic anti-inflammatory activities, was shown to suppress formation block expression of COX-2 synthase-1. Here, we identified synthase-1 as molecular target...
Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), the most relevant eicosanoid promoting inflammation and tumorigenesis, is formed by cyclooxygenases (COXs) PGE<sub>2</sub> synthases from free arachidonic acid. Preparations of leaves <i>Salvia officinalis</i> are commonly used in folk medicine as an effective antiseptic anti-inflammatory remedy possess anticancer activity. Here, we demonstrate that a standard ethyl acetate extract <i>S. efficiently suppresses formation cell-free assay direct...
Proinflammatory leukotrienes (LTs) are produced by 5-lipoxygenase (5-LO) aided 5-LO-activating protein (FLAP). LT biosynthesis inhibitors currently under clinical investigation as treatments for respiratory and cardiovascular diseases. Here, we have revealed a sex bias in the efficiency of clinically relevant inhibitors, showing that their effects superior females. We found androgens cause these differences impeding LT-biosynthetic 5-LO/FLAP complex assembly. Lower doses FLAP inhibitor MK886...
The activity of protein kinase B (Akt)—a major promoting cell proliferation and survival—oscillates during the cycle. To investigate whether membrane phospholipids may regulate Akt phosphorylation thus activity, we monitored lipid profile nocodazole-synchronized mouse NIH 3T3 fibroblasts cycle by liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS). proportion sn -2-arachidonoyl-phosphatidylcholine (20:4-PC) inversely correlated with activity. Increasing cellular...
Microsomal prostaglandin E2 synthase (mPGES)-1 is responsible for the massive (PGE2) formation during inflammation. Increasing evidence reveals mPGES-1 inhibitors as a safe alternative to nonsteroidal anti-inflammatory drugs. The first selective recently entered clinical trials. Major challenges drug development have been high plasma protein binding of lead structures, interspecies discrepancies, nuisance inhibition, sophisticated enzyme assays, and limited structural information about...