A5052250280- Renin-Angiotensin System Studies
- Receptor Mechanisms and Signaling
- Nitric Oxide and Endothelin Effects
- Hormonal Regulation and Hypertension
- Congenital heart defects research
- RNA Research and Splicing
- RNA modifications and cancer
- Cancer-related gene regulation
- Protein Kinase Regulation and GTPase Signaling
- Computational Drug Discovery Methods
- PARP inhibition in cancer therapy
- ATP Synthase and ATPases Research
- Hippo pathway signaling and YAP/TAZ
- Acute Ischemic Stroke Management
- Advanced biosensing and bioanalysis techniques
- Epigenetics and DNA Methylation
- Retinoids in leukemia and cellular processes
- interferon and immune responses
- Estrogen and related hormone effects
- Kruppel-like factors research
- Atrial Fibrillation Management and Outcomes
- Developmental Biology and Gene Regulation
- Cardiac Fibrosis and Remodeling
- Protease and Inhibitor Mechanisms
- Cell Adhesion Molecules Research
Charité - Universitätsmedizin Berlin
2003-2014
Institute of Pharmacology
2012
Sahlgrenska University Hospital
2010
Max Delbrück Center
2010
Heidelberg University
2010
Max Planck Institute for Molecular Genetics
2006
Memorial Sloan Kettering Cancer Center
2006
University Hospital Schleswig-Holstein
2004
University of Lübeck
2004
Kiel University
2004
A human renin/prorenin receptor (RER) has recently been cloned. To gain insight into the molecular function of RER, we studied its signal transduction mechanisms. Initially, found a ubiquitous and intracellular expression pattern RER. Consistently, observed several transcriptional start sites high promoter activity We could identify transcription factor promyelocytic zinc finger (PLZF) protein as direct interaction partner C-terminal domain RER by yeast 2-hybrid screening...
Angiotensin II type 2 (AT(2)) receptors can be regarded as an endogenous repair system, because the AT(2) receptor is upregulated in tissue damage and mediates protection. A potential therapeutic use of this system has only recently come within reach through synthesis first selective, orally active, nonpeptide agonist, compound 21 (C21; dissociation constant for receptor: 0.4 nM; angiotensin 1 >10,000 nM). This study tested stimulation with C21 a future approach inhibition proinflammatory...
Synthesis and maturation of G protein-coupled receptors are complex events that require an intricate combination processes including protein folding, posttranslational modifications, transport through distinct cellular compartments. Little is known concerning the regulation receptor from endoplasmic reticulum to cell surface.Here we show cytoplasmatic carboxy-terminal angiotensin AT2 (AT2R) acts independently as reticulum-export signal. Using a yeast two-hybrid system, identified Golgi...
Ceftriaxone has been reported to reduce neuronal damage in amyotrophic lateral sclerosis and an in-vitro model of ischaemia through increased expression activity the glutamate transporter, GLT1. We tested effects ceftriaxone on mortality, neurological outcome, infarct size experimental stroke rats looked for underlying mechanisms.Male normotensive Wistar received (200 mg/kg intraperitoneal) as a single injection 90 min after middle cerebral artery occlusion (90 with reperfusion). Forty-eight...
Objectives Inhibition of (pro)renin receptor activation was demonstrated to inhibit or even abolish the development end-organ damage in animal models. The new renin inhibitor, aliskiren, markedly increases plasma concentration ligands prorenin and patients. effects inhibitors on signal transduction cascade are currently unknown. Results Our results indicate that were equally potent by decreasing mRNA, increasing phosphatidylinositol-3 kinase p85α mRNA augmenting viable cell number,...
Stroke is one of the major medical burdens in industrialized countries. Animal experiments indicate that blockade angiotensin AT1 receptor (AT1R) improves neurological outcome after cerebral ischemia. These protective effects are partially mediated by AT2 (AT2R). The transcription factor promyelocytic leukemia zinc finger (PLZF) was identified as a direct adapter protein AT2R. Furthermore, our group able to demonstrate PLZF also directly binds and mediates human (pro)renin [(P)RR] which...
Cathepsin G (CTSG), a serine protease released from activated neutrophils, may cause platelet activation, leading to intravascular thrombosis, thus contributing cardiovascular and cerebrovascular disease. Applying the candidate gene approach, we screened 5′-flanking region entire coding of CTSG for genetic variation by using polymerase chain reaction/single-strand conformation polymorphism analysis 96 patients at high risk myocardial infarction (MI). We identified 4 polymorphisms in (G-618C,...
Background Human endothelin-converting enzyme (ECE)-1, the key in endothelin biosynthesis, shows broad cell and tissue expression within cardiovascular system. Expression of ECE-1c, which represents major ECE-1 isoform, is directed by an alternative promoter, but mechanisms ECE-1c promoter regulation are largely unknown. As transcription initiated from several start sites, we hypothesized that functions as a housekeeping promoter. Objective To investigate putative function vascular...
Genetic factors strongly contribute to the pathogenesis of sporadic Alzheimer's disease (AD). Nevertheless, genome-wide association studies only yielded single nucleotide polymorphism loci moderate importance. In contrast, microsatellite repeats are functionally less characterized structures within our genomes. Previous work has shown that endothelin-converting enzyme-1 (ECE-1) is able reduce amyloid β content. Here we demonstrate a CpG-CA repeat human ECE-1c promoter highly polymorphic,...
Isoform-specific expression of endothelin-converting enzyme (ECE)-1, the major big endothelin-processing enzyme, is controlled by alternative promoters. Signaling pathways and transcriptional mechanisms ECE-1 mRNA are largely unknown. To investigate isoform after protein kinase C (PKC) activation, we used phorbol 12-myristate 13-acetate (PMA) to stimulate primary cultured human umbilical vein endothelial cells related EA.hy926 cell line. ECE-1a was up-regulated (approximately 3-fold),...
Human ECE‐1 is expressed in four isoforms with different tissue distribution and its mRNA protein levels are altered under certain pathophysiological conditions. To investigate the transcriptional regulation of ECE‐1, we studied regulatory region ECE‐1c, major isoform. A genomic clone comprising complete human gene including putative ECE‐1c‐specific promoter was obtained. Up to 968 bp upstream c‐specific translation initiation start codon several serial deletion mutants were subcloned into a...
Nitric oxide (NO) and endothelin-1 (ET-1) are known to play a major role in renal vascular pathophysiology exhibit close interaction with ET-1, stimulating NO production; turn inhibits ET-1 expression. Our objectives were (1) establish novel transgenic mouse model facilitating expression assessment vivo, (2) validate this by assessing prepro-ET-1 promoter activity mice embryos means of our comparing sites well-established data on fetal development (3) investigate ET-NO different structures...
The homeobox transcription factor Nkx2-5 and the zinc metalloprotease endothelin-converting enzyme-1 (ECE-1) are essential for cardiac development. Here, we demonstrate first time a functional link between ECE-1. In transiently transfected rat H9c2 cardiomyoblasts, alternative promoters specific ECE-1a, ECE-1b, ECE-1c activated by coexpression. Lack of consensus sequence binding within promoter mutational analyses sequences identified in ECE-1a ECE-1b promoters, respectively, reveal an...
Cleavage of big endothelins (ETs) by endothelin-converting enzymes (ECEs) represents the final step in biosynthesis ETs. ECE-1 is expressed predominantly endothelial cells and exists two isoforms, termed α β, differing their 5′ termini. We have recently shown that isoform-specific mRNA expression directed alternative promoters. To investigate possible mechanisms transcriptional regulation ECE-1, we stimulated E.A. hy 926 with phorbol ester found a greater than threefold increase ECE-1β at...
The (pro)renin receptor [(P)RR] is crucial for cardio-renal pathophysiology. distinct molecular mechanisms of this are still incompletely understood. (P)RR able to interact with different signalling proteins such as promyelocytic leukemia zinc finger protein (PLZF) and Wnt receptors. Moreover, domains the essential V-ATPase activity. V-ATPase- Wnt-mediated effects imply constitutive, i.e., (pro)renin-independent functions (P)RR. Regarding ligand-dependent signalling, role prorenin...