A5016290453- Endoplasmic Reticulum Stress and Disease
- Cancer, Lipids, and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Inflammatory mediators and NSAID effects
- Drug-Induced Hepatotoxicity and Protection
- Selenium in Biological Systems
- Autophagy in Disease and Therapy
- Mass Spectrometry Techniques and Applications
- Silymarin and Mushroom Poisoning
- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Estrogen and related hormone effects
- Genetics, Aging, and Longevity in Model Organisms
- Curcumin's Biomedical Applications
- Polyamine Metabolism and Applications
- Ferroptosis and cancer prognosis
- Sphingolipid Metabolism and Signaling
- Protein Degradation and Inhibitors
- Eicosanoids and Hypertension Pharmacology
- Natural product bioactivities and synthesis
- Asthma and respiratory diseases
- Paraoxonase enzyme and polymorphisms
- Antioxidant Activity and Oxidative Stress
- Pluripotent Stem Cells Research
- CRISPR and Genetic Engineering
Universität Innsbruck
2020-2025
Friedrich Schiller University Jena
2019-2021
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...
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...
Abstract Cell death programs such as apoptosis and ferroptosis are associated with aberrant redox homeostasis linked to lipid metabolism membrane function. Evidence for cross-talk between these is emerging. Here, we show that cytotoxic stress channels polyunsaturated fatty acids via lysophospholipid acyltransferase 12 into phospholipids become susceptible peroxidation under additional stress. This reprogramming altered acyl-CoA synthetase isoenzyme expression caused by a decrease in growth...
Proteomics and metabolomics are essential in systems biology, simultaneous proteo-metabolome liquid–liquid extraction (SPM-LLE) allows isolation of the metabolome proteome from same sample. Since is present as a pellet SPM-LLE, it must be solubilized for quantitative proteomics. Solubilization critical factors information obtained at level. In this study, we investigated performance two surfactants (sodium deoxycholate (SDC), sodium dodecyl sulfate (SDS)) urea terms coverage efficiency an...
Glutathione peroxidase 2 (GPx2) is one of the five selenoprotein GPxs having a selenocysteine in active center. GPx2 strongly expressed gastrointestinal epithelium, as another isoform, GPx1, though with different localization pattern. Both are redox-active enzymes that important for reduction hydroperoxides. Studies on GPx2-deficient mice and human HT-29 cells stable knockdown (kd) revealed higher basal IL-1β-induced expression NF-κB target genes vivo vitro. The activation IKK-IκBα-NF-κB...
Article10 December 2020Open Access Transparent process Tnfaip2/exoc3-driven lipid metabolism is essential for stem cell differentiation and organ homeostasis Sarmistha Deb orcid.org/0000-0002-2702-3881 Leibniz Institute on Aging – Fritz Lipmann e.V., Jena, Germany Search more papers by this author Daniel A Felix Philipp Koch orcid.org/0000-0003-2825-7943 Maharshi Krishna orcid.org/0000-0003-0026-6194 Karol Szafranski orcid.org/0000-0001-6391-1766 Katrin Buder Mara Sannai Marco Groth...
Rationale:Silybum marianum is used to protect against degenerative liver damage. The molecular mechanisms of its bioactive component, silybin, remained enigmatic, although membrane-stabilizing properties, modulation membrane protein function, and metabolic regulation have been discussed for decades. Methods: Experiments were performed with hepatocyte cell lines primary monocytes in vitro under both basal stressed conditions, mice vivo. Quantitative lipidomics was detect changes phospholipids...
Polypharmacological targeting of lipid mediator networks offers potential for efficient and safe anti-inflammatory therapy. Because the diversity its biological targets, curcumin (1a) has been viewed as a privileged structure bioactivity or, alternatively, pan-assay interference (PAIN) compound. Curcumin actually few high-affinity most remarkable ones being 5-lipoxygenase (5-LOX) microsomal prostaglandin E2 synthase (mPGES)-1. These enzymes are critical production pro-inflammatory...
α-Tocopherol-13'-carboxychromanol (α-T-13'-COOH) is an endogenously formed bioactive α-tocopherol metabolite that limits inflammation and has been proposed to exert lipid metabolism-regulatory, pro-apoptotic, anti-tumoral properties at micromolar concentrations. The mechanisms underlying these cell stress-associated responses are, however, poorly understood. Here, we show the induction of G0/G1 cycle arrest apoptosis in macrophages triggered by α-T-13'-COOH associated with suppressed...
Endogenous long-chain metabolites of vitamin E (LCMs) mediate immune functions by targeting 5-lipoxygenase (5-LOX) and increasing the systemic concentrations resolvin E3, a specialized proresolving lipid mediator. SAR studies on semisynthesized analogues highlight α-amplexichromanol (
Physiological selenium (Se) levels counteract excessive inflammation, with selenoproteins shaping the immunoregulatory cytokine and lipid mediator profile. How exactly differentiation of monocytes into macrophages influences expression selenoproteome in concert Se supply remains obscure. THP-1 were differentiated phorbol 12-myristate 13-acetate (PMA) (i) selenoproteins, (ii) markers, (iii) activity NF-κB NRF2, as well (iv) profiles analyzed. affected a heterogeneous manner. GPX4 was...
Abstract Tumours face tryptophan (Trp) depletion, but the mechanisms sustaining protein biosynthesis under Trp stress remain unclear. We report that increases levels of translation repressor EIF4EBP1. Yet, at same time, EIF4EBP1 is selectively phosphorylated by metabolic master regulator MTORC1 kinase, preventing from inhibiting translation. activity unexpected because absence amino acids typically linked with inhibition. EIF4EBP1-sensitive in starved cells sustained EGFR and RAS signalling...
Abstract Silybum marianum is used to protect against degenerative liver damage. The molecular mechanisms of its bioactive component, silybin, remained enigmatic, although membrane-stabilizing properties, modulation membrane protein function, and metabolic regulation have been discussed for decades. Here, we show that specifically the stereoisomer silybin A decreases triglyceride levels lipid droplet content, while enriching major phospholipid classes maintaining a homeostatic composition in...
Abstract Proteo-metabolomics is essential in systems biology and simultaneous proteo-metabolome extraction by liquid-liquid (SPM-LLE) allows of the metabolome proteome from same sample. Since present as a pellet SPM-LLE it must be solubilized for quantitative proteomics. Solubilization critical factor information that can obtained at level. In this study, we investigated performance two surfactants (sodium deoxycholate (SDC), sodium dodecyl sulfate (SDS)) urea with respect to coverage...