A5025694365- Animal testing and alternatives
- Redox biology and oxidative stress
- Selenium in Biological Systems
- Viral-associated cancers and disorders
- Animal Disease Management and Epidemiology
- Glutathione Transferases and Polymorphisms
- Trace Elements in Health
- Eosinophilic Disorders and Syndromes
- Sperm and Testicular Function
- Molecular Biology Techniques and Applications
- Mitochondrial Function and Pathology
- Viral gastroenteritis research and epidemiology
- Lymphoma Diagnosis and Treatment
- Virus-based gene therapy research
- Helicobacter pylori-related gastroenterology studies
- Diabetes Treatment and Management
- Metabolism, Diabetes, and Cancer
- Heavy Metal Exposure and Toxicity
- Receptor Mechanisms and Signaling
- Sulfur Compounds in Biology
- Animal Behavior and Welfare Studies
- RNA Interference and Gene Delivery
- Mast cells and histamine
- Endoplasmic Reticulum Stress and Disease
- Microbial infections and disease research
Helmholtz Zentrum München
2012-2024
Ruhr University Bochum
2014
Center for Environmental Health
2011
Ludwig-Maximilians-Universität München
2011
Giessen School of Theology
2007
Kerckhoff Klinik
2007
University of Massachusetts Chan Medical School
2007
Max Planck Institute for Biophysical Chemistry
2007
Institute of Groundwater Ecology
2004-2007
Urologische Klinik München
1997-2001
Oxygen radicals regulate many physiological processes, such as signaling, proliferation, and apoptosis, thus play a pivotal role in pathophysiology disease development. There are at least two thioredoxin reductase/thioredoxin/peroxiredoxin systems participating the cellular defense against oxygen radicals. At present, relatively little is known about contribution of individual enzymes to redox metabolism different cell types. To begin address this question, we generated characterized mice...
Two distinct thioredoxin/thioredoxin reductase systems are present in the cytosol and mitochondria of mammalian cells. Thioredoxins (Txn), main substrates thioredoxin reductases (Txnrd), involved numerous physiological processes, including cell-cell communication, redox metabolism, proliferation, apoptosis. To investigate individual contribution mitochondrial (Txnrd2) cytoplasmic (Txnrd1) vivo, we generated a mouse strain with conditionally targeted deletion Txnrd1. We show here that...
A 34 kD selenoprotein purified from rat testis was identified as a specific sperm nuclei glutathione peroxidase (snGPx) with similar properties to phospholipid hydroperoxide (PHGPx). The determination of its primary structure by analysis first N-terminal amino acids, database search, polymerase chain reaction, and sequencing the cDNA showed that it differs PHGPx in sequence. This sequence, which is encoded for an alternative exon intron gene, shows more than 50% homology protamine sequences...
The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is regarded as the major molecular target of selenodeficiency in rodents, accounting for most histopathological and structural abnormalities testicular tissue male germ cells. PHGPx exists a cytosolic form, mitochondrial nuclear form (nPHGPx) predominantly expressed late spermatids spermatozoa. Here, we demonstrate that mice with targeted deletion nPHGPx gene were, unlike full knockout (KO) PHGPx, not only viable but...
The product of the proto-oncogene c-myc (myc) is a potent activator cell proliferation. In Burkitt lymphoma (BL), human B-cell tumor, myc consistently found to be transcriptionally activated by chromosomal translocation. mechanisms which promotes cycle progression in B-cells not known. As model for activation BL cells, we have established EBV-EBNA1 positive line, P493-6, expressed under control tetracycline regulated promoter. If expression switched off, P493-6 cells arrest G0/G1 presence...
Abstract Pancreatic ductal adenocarcinoma (PDAC) and its precursor lesions, pancreatic intraepithelial neoplasia (PanIN), display a phenotype. However, there is evidence in genetically defined mouse models for PDAC harbouring mutated kras under the control of pancreas‐specific promoter that cancer might arise centroacinar‐acinar region, possibly through process acinar‐ductal metaplasia (ADM). In order to further elucidate this model development, an extensive expression analysis molecular...
The thioredoxin-dependent system is an essential regulator of cellular redox balance. Since oxidative stress has been linked with neurodegenerative disease, we studied the roles thioredoxin reductases in brain using mice nervous (NS)-specific deletion cytosolic (Txnrd1) and mitochondrial (Txnrd2) reductase. While NS-specific Txnrd2 null develop normally, lacking Txnrd1 NS were significantly smaller displayed ataxia tremor. A striking patterned cerebellar hypoplasia was observed....
Background— Excessive formation of reactive oxygen species contributes to tissue injury and functional deterioration after myocardial ischemia/reperfusion. Especially, mitochondrial are capable opening the permeability transition pore, a harmful event in cardiac Thioredoxins key players defense against oxidative stress. Mutations thioredoxin reductase (thioredoxin reductase-2, Txnrd2) gene have been recently identified cause dilated cardiomyopathy patients. Here, we investigated whether is...
Selenium exerts many, if not most, of its physiological functions as a selenocysteine moiety in proteins. Selenoproteins are involved many biochemical processes including regulation cellular redox state, calcium homeostasis, protein biosynthesis, and degradation. A neurodevelopmental syndrome called progressive cerebello-cortical atrophy (PCCA) is caused by mutations the synthase gene, SEPSECS, demonstrating that selenoproteins essential for human brain development. While we have shown...
Animal welfare requires the adequate housing of animals to ensure health and well-being. The application environmental enrichment is a way improve well-being laboratory animals. However, it important know whether these items can be incorporated in experimental mouse husbandry without creating divide between past future results. Previous small-scale studies have been inconsistent throughout literature, not yet completely understood how might endanger comparability results scientific...
ABSTRACT Both Epstein-Barr viral nuclear antigen 2 (EBNA2) and activated Notch transactivate genes by interacting with the transcription factor RBP-Jκ. The protein EBNA2 may hence be regarded as a functional equivalent of an receptor. Until now, nothing has been known about physiological role signaling in B cells. Here we investigated whether can induce same phenotypic changes Burkitt's lymphoma An estrogen receptor fusion intracellular part mouse 1 (mNotch1-IC), mimicking presence...
Abstract Inducible and tissue‐specific gene inactivation in mice has become a powerful tool to bypass embryonic postnatal lethality of knockout mice. The most frequently used inducible system is based on Cre recombinase fused either one or two mutated estrogen receptor ligand binding domains, thus rendering function tamoxifen‐dependent. To achieve Cre‐mediated given gene, 4‐OH tamoxifen (4‐OHT) dissolved alcohol and/or oil usually administered by repeated intraperitoneal (i.p.) injections....
Background Ubiquitous deletion of thioredoxin reductase 2 ( Txnrd2 ) in mice is embryonically lethal and associated with abnormal heart development, while constitutive, heart‐specific inactivation leads to dilated cardiomyopathy perinatal death. The significance aging cardiomyocytes, however, has not yet been examined. Methods Results tamoxifen‐inducible α MHC‐MerCreMer transgene was used inactivate lox P‐flanked alleles adult mice. Hearts isolated mitochondria from aged knockout were...
One limitation to housing rodents in individually ventilated cages (IVCs) is the ineffectiveness of traditional health monitoring programs that test soiled bedding sentinels every quarter. Aerogen transmission does not occur with this method. Moreover, numerous pathogens uncertain, and sentinel susceptibility various varies. A novel method using particle collection from samples exhaust air was developed study which also systematically compared routine sentinels. We used our screen these for...
The NF-κB transcription factor is activated by a wide variety of stimuli, including phorbol esters such as 12-O-tetradecanoylphorbol-13-acetate. In its inactive state, sequestered in the cytoplasm tethered to an inhibitor protein, IκB. Activation comprises rapid phosphorylation IκB-α at N-terminal sites, which presumably marks for proteolytic degradation and leads release into nucleus. addition, constitutively phosphorylated C terminus, may be prerequisite proper IκB function. Protein kinase...
Abstract The selenoprotein phospholipid hydroperoxide glutathione peroxidase (PHGPx) is present in at least three different isoforms testis: as a cytosolic, mitochondrial, and nuclear protein. We have recently shown that sperm nucleus-specific (snGPx) identical to the mitochondrial cytosolic forms of PHGPx apart from its N-terminus. This arginine-rich N-terminus snGPx, reminiscent protamines, encoded by an alternative exon located first intron gene responsible for localisation chromatin...
The German Mouse Clinic (GMC) is a large scale phenotyping center where mouse mutant lines are analyzed in standardized and comprehensive way. result an almost complete picture of the phenotype line--a systemic view. At GMC, expert scientists from various fields research work close cooperation with clinicians side by at one location. screens comprise following areas: allergy, behavior, clinical chemistry, cardiovascular analyses, dysmorphology, bone cartilage, energy metabolism, eye vision,...
Many cell lines are sensitive to growth at low density and undergo apoptosis induced by oxidative stress if the is decreased below a critical threshold. In stable transfection experiments this density-dependent may be limiting factor, since during drug selection falls threshold, precluding outgrowth of transfected clones. We describe here simple protocol for establishment stably human B making use protective action antioxidants. The includes: (i) seeding cells in medium supplemented with...
Over recent years, the use of individually ventilated cage (IVC) rack systems in laboratory rodent facilities has increased. Since every an IVC may be assumed to a separate microbiological unit, comprehensive monitoring animals kept IVCs become challenging task, which addressed by appropriate sentinel mice. Traditionally, these sentinels have been exposed soiled bedding but more recently, concept exposure exhaust air considered. The work reported here was aimed firstly at testing efficiency...
Accurate knowledge of the health status experimental animals is pivotal to high scientific and ethical standards in biomedical research. Individually ventilated cages (IVCs) are becoming predominant system for housing laboratory mice, as they prevent cage-to-cage infections. However, this feature constitutes a major drawback hygienic monitoring mouse colonies, traditional screening programs build on reliable transmission infectious agents from sentinel mice commonly tested representatives...
Abstract During β-adrenergic stimulation of brown adipose tissue (BAT), p38 phosphorylates the activating transcription factor 2 (ATF2) which then translocates to nucleus activate expression Ucp1 and Pgc-1α . The mechanisms underlying ATF2 target activation are unknown. Here we demonstrate that p62 (Sqstm1) binds orchestrate enhancer promoter. P62 Δ69-251 mice show reduced with impaired genomic binding. Modulation through regulation signaling is demonstrated in vitro vivo mice, global −/−...