A5052788301- Selenium in Biological Systems
- Thyroid Disorders and Treatments
- Trace Elements in Health
- Growth Hormone and Insulin-like Growth Factors
- Heavy Metal Exposure and Toxicity
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Redox biology and oxidative stress
- Ion channel regulation and function
- Birth, Development, and Health
- Amino Acid Enzymes and Metabolism
- Neuroscience of respiration and sleep
- Glutathione Transferases and Polymorphisms
- Organoselenium and organotellurium chemistry
- Thyroid Cancer Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Astronomical and nuclear sciences
- Estrogen and related hormone effects
- Metalloenzymes and iron-sulfur proteins
- Mitochondrial Function and Pathology
- Neonatal Health and Biochemistry
- Endoplasmic Reticulum Stress and Disease
- Digestive system and related health
- Mercury impact and mitigation studies
- Nitric Oxide and Endothelin Effects
University of Bonn
2016-2025
University Hospital Bonn
2018-2025
University Children's Hospital Tübingen
2022
Universitätsklinikum Tübingen
2017-2022
Charité - Universitätsmedizin Berlin
2007-2019
Indian Institute of Science Bangalore
2016
Centre Hospitalier Universitaire d'Angers
2014
Bicêtre Hospital
2014
University of Tübingen
1980-2013
Endokrinologikum
2005-2011
Selenoprotein P (SePP), the major selenoprotein in plasma, has been implicated selenium transport, detoxification or antioxidant defence. We generated SePP-knockout mice that were viable, but exhibited reduced growth and developed ataxia. Selenium content was elevated liver, low plasma other tissues, selenoenzyme activities changed accordingly. Our data reveal SePP plays a pivotal role delivering hepatic to target tissues.
The selenoenzyme glutathione peroxidase 4 (Gpx4) is an essential mammalian peroxidase, which protects cells against detrimental lipid peroxidation and governs a novel form of regulated necrotic cell death, called ferroptosis. To study the relevance Gpx4 another vitally important selenoprotein, cytosolic thioredoxin reductase (Txnrd1), for liver function, mice with conditional deletion in hepatocytes were studied, along those lacking Txnrd1 selenocysteine (Sec) tRNA (Trsp) hepatocytes. Unlike...
The human genome contains 25 genes coding for selenocysteine-containing proteins (selenoproteins). These are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions designated according to these functions: TXNRD1, TXNRD2, and TXNRD3 (thioredoxin reductases), GPX1, GPX2, GPX3, GPX4, GPX6 (glutathione peroxidases), DIO1, DIO2, DIO3 (iodothyronine deiodinases), MSRB1 (methionine sulfoxide reductase B1), SEPHS2 (selenophosphate synthetase...
Cerebral selenium (Se) deficiency is associated with neurological phenotypes including seizures and ataxia. We wanted to define whether neurons require selenoprotein expression which selenoproteins are most important, explore the possible pathomechanism. Therefore, we abrogated of all in by genetic inactivation tRNA[Ser](Sec) gene. was significantly diminished mutants, histological analysis revealed progressive neurodegeneration. Developing interneurons failed specifically express...
Liver-specific inactivation of Trsp, the gene for selenocysteine tRNA, removes SePP (selenoprotein P) from plasma, causing serum selenium levels to fall 298 μg/l 50 and kidney decrease 36% wild-type levels. Likewise, glutathione peroxidase activities decreased in plasma 43% 18% respectively This agrees nicely with data knockout mice, supporting a transport role hepatically expressed SePP. However, brain remain unaffected neurological defects do not occur liver-specific Trsp while mice suffer...
Thyroid hormone transport into cells requires plasma membrane proteins. Mutations in one of these, monocarboxylate transporter 8 (MCT8), have been identified as underlying cause for the Allan–Herndon–Dudley syndrome, an X-linked mental retardation which patients also present with abnormally high 3′,3,5-triiodothyronine (T 3 ) levels. Mice deficient Mct8 replicate thyroid abnormalities observed human condition. However, no neurological deficits described mice lacking . Therefore, we subjected...
Although dietary selenium (Se) deficiency results in phenotypes associated with selenoprotein depletion various organs, the brain is protected from Se loss. To address basis for critical role of function, we carried out comparative gene expression analyses complete selenoproteome and biosynthetic factors. Using Allen Brain Atlas, evaluated 159 regions adult mouse provided experimental selected selenoproteins. All 24 mRNAs were expressed brain. Most strikingly, neurons olfactory bulb,...
The acute-phase response (APR) is characterized by an impaired metabolism of the essential trace element selenium (Se). Moreover, low-Se concentrations correlate to mortality risk in sepsis. Therefore, we analyzed expression central Se transport and storage protein selenoprotein P (Sepp1) during APR mice. Serum Sepp1 declined parallel after injection lipopolysaccharide 50 39% control-injected littermates, respectively. This negative proceeded largely independent from hepatic transcript...
SePP (selenoprotein P) is central for selenium transport and distribution. Targeted inactivation of the Sepp gene in mice leads to reduced content plasma, kidney, testis brain. Accordingly, activities selenoenzymes are Sepp−/− organs. Male infertile. Unlike deficiency, deficiency neurological impairment with ataxia seizures. Hepatocyte-specific selenoprotein biosynthesis reduces plasma kidney levels similarly mice, but does not result impairment, suggesting a physiological role locally...
Ferroptosis has emerged as an attractive strategy in cancer therapy. Understanding the operational networks regulating ferroptosis may unravel vulnerabilities that could be harnessed for therapeutic benefit. Using CRISPR-activation screens hypersensitive cells, we identify selenoprotein P (SELENOP) receptor, LRP8, a key determinant protecting MYCN-amplified neuroblastoma cells from ferroptosis. Genetic deletion of LRP8 leads to result insufficient supply selenocysteine, which is required...
Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention begins with the uptake of Sec carrier, selenoprotein P (SELENOP). Following uptake, released from SELENOP metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate selenophosphate synthetase 2 (SEPHS2), which provides essential selenium donor, (H2SePO3-), biosynthesis Sec-tRNA. Here, we discovered an alternative pathway in mediated by peroxiredoxin 6 (PRDX6), independent SCLY....
Members of the ciliary neurotrophic factor (CNTF)/leukemia inhibitory (LIF)/cardiotrophin gene family are potent survival factors for embryonic and lesioned motoneurons. These act via receptor complexes involving gp130 LIFR-beta ligand binding leads to activation various signaling pathways, including phosphorylation Stat3. The role Stat3 in neuronal was investigated mice by Cre-mediated ablation Cre is expressed under neurofilament light chain (NF-L) promoter, starting around E12 when these...
Cellular thyroid hormone uptake and efflux are mediated by transmembrane transport proteins. One of these, monocarboxylate transporter 8 (MCT8) is mutated in Allan-Herndon-Dudley syndrome, a severe mental retardation associated with abnormal constellations. Since mice deficient Mct8 exhibit milder neurological phenotype than patients, we hypothesized that alternative transporters may compensate murine brain cells for the lack Mct8. Using qPCR, Western Blot, immunocytochemistry, investigated...