A5075089213- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Chronic Kidney Disease and Diabetes
- Signaling Pathways in Disease
- Calpain Protease Function and Regulation
- Cell Adhesion Molecules Research
- Osteoarthritis Treatment and Mechanisms
- Atrial Fibrillation Management and Outcomes
- Cardiac Fibrosis and Remodeling
- Bone Metabolism and Diseases
- Metabolism, Diabetes, and Cancer
- Enzyme Structure and Function
- Blood Coagulation and Thrombosis Mechanisms
- Cardiovascular Function and Risk Factors
- Inflammatory mediators and NSAID effects
- S100 Proteins and Annexins
- Cellular transport and secretion
- Natural product bioactivities and synthesis
- Plant Ecology and Taxonomy Studies
- Neurobiology and Insect Physiology Research
- Calcium signaling and nucleotide metabolism
- Neurosurgical Procedures and Complications
- Oral microbiology and periodontitis research
- Renal Diseases and Glomerulopathies
- Biochemical and Structural Characterization
Sanofi (Germany)
2011-2021
Dermatologikum Hamburg
2020
Thor Technologies (United States)
2011
Kiel University
2002-2006
University of Bonn
1999-2002
University of Konstanz
2000-2002
Interleukin-6 (IL-6) activates cells by binding to the membrane-bound IL-6 receptor (IL-6R) and subsequent formation of a glycoprotein 130 homodimer. Cells that express 130, but not IL-6R, can be activated soluble IL-6R which is generated shedding from cell surface or alternative splicing. Here we show cholesterol depletion with methyl-beta-cyclodextrin increases independent protein kinase C activation thus differs phorbol ester-induced shedding. Contrary depletion, enrichment did increase...
Increased Jagged1 in pericentral hepatocytes causes liver fibrosis response to hepatocyte TLR4–NF-κB pathway activation NASH.
OBJECTIVE Elevated glycolytic enzymes in renal glomeruli correlated with preservation of function the Medalist Study, individuals ≥50 years type 1 diabetes. Specifically, pyruvate kinase M2 (PKM2) activation protected insulin-deficient diabetic mice from hyperglycemia-induced glomerular pathology. This study aims to extend these findings a separate cohort and 2 diabetes discover new circulatory biomarkers for protection through proteomics metabolomics Medalists’ plasma. We hypothesize that...
Unlike most other matrix metalloproteinases (MMPs) MMP-19 is expressed in undifferentiated basal keratinocytes of healthy human skin. The keratinocyte cell line HaCaT, which like constitutively expresses MMP-19, down-regulated the expression at high calcium concentrations. Calcium-regulation occurred through E-cadherin mediated cell-cell contacts because neutralizing anti-E-cadherin antibodies restored calcium. Overexpression HaCaT cells (HaCaT-WT) increased cellular proliferation, as well...
Matrix metalloproteinase-19 (MMP19) affects cell proliferation, adhesion, and migration in vitro but its physiological role vivo is poorly understood. To determine the function of MMP19, we generated mice deficient for MMP19 by disrupting catalytic domain mmp19 gene. Although MMP19-deficient do not show overt developmental morphological abnormalities they display a distinct phenotype. In model contact hypersensitivity (CHS) showed impaired T cell-mediated immune reaction that was...
Cathepsin A (CatA) is a serine carboxypeptidase distributed between lysosomes, cell membrane, and extracellular space. Several peptide hormones including bradykinin angiotensin I have been described as substrates. Therefore, the inhibition of CatA has potential for beneficial effects in cardiovascular diseases. Pharmacological by natural product ebelactone B increased renal levels prevented development salt-induced hypertension. However, so far no small molecule inhibitors with oral...
Type 2 diabetes (T2D) is an independent risk factor for atrial fibrillation (AF) and stroke. The serine protease cathepsin A (CatA) up-regulated in plays important role the degradation of extracellular peptides. This study sought to delineate CatA development remodelling under diabetic conditions. Zucker Diabetic Fatty rats (ZDF) were treated with vehicle (n = 20) or CatA-inhibitor (SAR; 50 mg/kg; n 20), compared age-matched non-diabetic littermates (Ctr, 20). Left-atrial (LA) emptying...
Abstract We have previously reported the isolation of human matrix metalloproteinase (MMP)-19 (also referred to as RASI) from a synovium patient suffering rheumatoid arthritis and its expression at cell surface activated PBMC. In this study, we analyzed regulation MMP-19 in several lines blood-derived cells. Among analyzed, is largely expressed by lung fibroblasts well myeloid THP-1 HL-60. After fractionating PBMC into CD14− CD14+ populations found that only latter one expresses MMP-19....
Myocardial infarction (MI) is a major cause of heart failure. The carboxypeptidase cathepsin A novel target in the treatment cardiac We aim to show that recently developed inhibitors protease attenuate post-MI Mice were subjected permanent left anterior descending artery (LAD) ligation or sham operation. 24 h post–surgery, LAD-ligated animals treated with daily doses inhibitor SAR1 placebo. After 4 weeks, three groups (sham, MI-placebo, MI-SAR1) evaluated. Compared sham-operated animals,...
In the heart, serine carboxypeptidase cathepsin A (CatA) is distributed between lysosomes and extracellular matrix (ECM). CatA-mediated degradation of peptides may contribute to ECM remodeling left ventricular (LV) dysfunction. Here, we aimed evaluate effects CatA overexpression on LV remodeling. proteomic analysis secretome adult mouse cardiac fibroblasts upon digestion by identified antioxidant enzyme superoxide dismutase (EC-SOD) as a novel substrate CatA, which decreased EC-SOD abundance...
The lysosomal serine carboxypeptidase CatA has a very important and well-known structural function as well a, so far, less explored catalytic function. A complete loss of the protein results in storage disease galactosialidosis caused by intralysosomal degradation β-galactosidase neuraminidase 1. However, mice with catalytically inactive enzyme show no signs this disease. This observation establishes clear distinction between functions enzyme. Recently, several classes orally bioavailable...
Cathepsin A (CTSA) is a lysosomal carboxypeptidase present at the cell surface and secreted outside cell. Additionally, CTSA binds to β-galactosidase neuraminidase 1 protect them from degradation. has gained attention as drug target for treatment of cardiac hypertrophy heart failure. Here, we investigated impact on murine proteome in mouse model cardiomyocyte-specific human overexpression using liquid chromatography-tandem mass spectrometry conjunction with an isotopic dimethyl labeling...
After myocardial infarction, remote ventricular remodeling and atrial cardiomyopathy progress despite successful revascularization. In a rat model of ischemia/reperfusion, pharmacological inhibition the protease activity cathepsin A initiated at time point reperfusion prevented extracellular matrix in atrium ventricle from infarcted area. This scenario was associated with preservation more viable myocardium prevention an arrhythmogenic functional substrate for fibrillation. Remote may...
Cellulite occurs in females and is a common condition of altered connective tissue matrix increased adipogenicity with visible dimples orange-peel appearance on the skins surface. Whilst advancements methods continue to help our understanding, attempts correct cellulite topically have yielded limited success. Various kinds non-invasive body contouring such as whole vibration been reported demonstrable improvements condition. The aim this study was evaluate volume reduction improvement judged...