A5050898125- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Peroxisome Proliferator-Activated Receptors
- Inflammatory mediators and NSAID effects
- Nitric Oxide and Endothelin Effects
- Diabetes Treatment and Management
- Cardiac electrophysiology and arrhythmias
- Cardiac Fibrosis and Remodeling
- Genetics and Neurodevelopmental Disorders
- Eicosanoids and Hypertension Pharmacology
- Sphingolipid Metabolism and Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Epigenetics and DNA Methylation
- Ion Channels and Receptors
- Heart Rate Variability and Autonomic Control
- Peptidase Inhibition and Analysis
- Nuclear Receptors and Signaling
- Heme Oxygenase-1 and Carbon Monoxide
- Genomics, phytochemicals, and oxidative stress
- Metabolism, Diabetes, and Cancer
- Advanced Glycation End Products research
- Vitamin K Research Studies
- Immune cells in cancer
- Cancer-related gene regulation
- Gestational Trophoblastic Disease Studies
- Genomics and Chromatin Dynamics
Medical University of Graz
2014-2023
JSS Academy of Higher Education and Research
2009
The NAD + precursor nicotinamide improves diastolic dysfunction caused by aging, hypertension, or metabolic syndrome in rodents.
Abstract Background In the extracellular environment, lysophosphatidic acid (LPA) species are generated via autotaxin (ATX)-mediated hydrolysis of lysophospholipid precursors. Members LPA family potent lipid mediators transmitting signals six different G protein-coupled receptors (LPAR1-6). The signaling axis is indispensable for brain development and function nervous system; however, during damage central system, levels can increase aberrant events counteract function. Here, we investigated...
Oxidation of LDL by the myeloperoxidase (MPO)-H2O2-chloride system is a key event in development atherosclerosis. The present study aimed at investigating interaction MPO with native and modified revealing posttranslational modifications on apoB-100 (the unique apolipoprotein LDL) vitro vivo. Using amperometry, we demonstrate that activity increases up to 90% when it adsorbed surface LDL. This phenomenon apparently reflected local structural changes observed circular dichroism. MS, further...
Gastrointestinal disorders with abdominal pain are associated central sensitization and psychopathologies that often exacerbated by stress. Here we investigated the impact of colitis induced dextran sulfate sodium (DSS) repeated water avoidance stress (WAS) on spontaneous nociception-related behavior molecular signaling in mouse brain. DSS increased mechanical sensitivity skin while both WAS enhanced thermal plantar skin. These manifestations were augmented c-Fos expression spinal cord,...
We describe the characterization of a gene for mild nonsyndromic autosomal recessive intellectual disability (ID) in two unrelated families, one from Austria, other Pakistan. Genome-wide single nucleotide polymorphism microarray analysis enabled us to define region homozygosity by descent on chromosome 17q25. Whole-exome sequencing and this an affected individual Austrian family identified 5 bp frameshifting deletion METTL23 gene. By means Sanger METTL23, nonsense mutation was detected...
Despite considerable efforts to improve treatment modalities for osteosarcoma (OS), patient survival remains poor mainly due pro-survival pathways in OS cells. Among others, prostaglandins (PGs) are the potent regulators of bone homoeostasis and pathophysiology. Therefore, present study aimed elucidate impact 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2, a stable PGD2 degradation product) on cell death/cell p53-deficient MG-63 Our findings show that 15d-PGJ2 induces generation reactive oxygen species...
Saxagliptin treatment has been associated with increased rate of hospitalization for heart failure in type 2 diabetic patients, though the underlying mechanism(s) remain elusive. To address this, we assessed effects saxagliptin on human atrial trabeculae, guinea pig hearts and cardiomyocytes. We found that primary target saxagliptin, dipeptidyl peptidase-4, is absent cardiomyocytes, yet internalized into cardiomyocytes impaired cardiac contractility via inhibition Ca2+/calmodulin-dependent...
The antioxidant 5-hydroxymethylfurfural (5-HMF) exerts documented beneficial effects in several experimental pathologies and is currently tested as an antisickling drug clinical trials. In the present study, we examined cardiovascular of 5-HMF elucidated mode action drug.
BackgroundProstaglandins (PGs), lipid autacoids derived from arachidonic acid, play a pivotal role during inflammation. PGD2 synthase is abundantly expressed in heart tissue and has recently been found to induce cardiomyocyte apoptosis. an unstable prostanoid metabolite; therefore the objective of present study was elucidate whether its final dehydration product, 15-deoxy-Δ12,14-PGJ2 (15d-PGJ2, at high levels ischemic myocardium) might cause damage.Methods resultsUsing specific (ant)agonists...
Peroxynitrite, a potent pro-inflammatory and cytotoxic species, interacts with variety of heme containing proteins. We addressed the question whether (i) interaction myeloperoxidase (MPO, an enzyme generating hypochlorous acid from hydrogen peroxide chloride ions) peroxynitrite affects clearance peroxynitrite, (ii) if could modulate chlorinating activity MPO. Our results show that this promotes decomposition highly reactive oxidant, whereby MPO Compound II (but not I) is formed. The...
Some oral anti-hyperglycemic drugs, including gliptins that inhibit dipeptidyl peptidase 4 (DPP4), have been linked to the increased risk of heart failure (HF) in type-2 diabetic patients. While cardiovascular safety trial, TECOS, revealed no link between sitagliptin and HF, a substantial 27% increase hospitalization for HF was observed patients treated with saxagliptin within SAVOR-TIMI 53 trial. A previous vitro study impairs Ca2+/calmodulin-dependent protein kinase II...
Lower heart rate is associated with better survival in patients multiple organ dysfunction syndrome (MODS), a disease mostly caused by sepsis. The benefits of reduction ivabradine during MODS are currently being investigated the MODIfY clinical trial. Ivabradine selective inhibitor pacemaker current If and since impaired lipopolysaccharide (LPS, endotoxin), trigger sepsis, we aimed to explore blocking potency under elevated endotoxin levels human atrial cardiomyocytes. Treatment myocytes...
Lysophosphatidic acid (LPA) species are a family of bioactive lipids that transmit signals via six cognate G protein-coupled receptors, which required for brain development and function the nervous system. LPA affects all cell types in can display beneficial or detrimental effects on microglia function. During earlier studies we reported treatment induces polarization towards neurotoxic phenotype. In present study investigated whether these alterations accompanied by induction specific...
The transcription factor forkhead box protein P2 (FOXP2) is a highly conserved key regulator of embryonal development. molecular mechanisms how FOXP2 regulates development, however, remain elusive. Using RNA sequencing, we identified the Wnt signaling pathway as target FOXP2-dependent transcriptional regulation. cell-based assays, show that activity regulated by coregulator β-catenin and contacts multiple regions within FOXP2. nuclear magnetic resonance spectroscopy, uncovered details these...
Sepsis has emerged as a global health burden associated with multiple organ dysfunction and 20% mortality rate in patients. Numerous clinical studies over the past two decades have correlated disease severity septic patients impaired heart variability (HRV), consequence of chronotropic response sinoatrial node (SAN) pacemaker activity to vagal/parasympathetic stimulation. However, molecular mechanism(s) downstream parasympathetic inputs not been investigated yet sepsis, particularly SAN....
Sepsis is a major cause of mortality in critically ill patients and associated with cardiac dysfunction, complication linked to immunological metabolic aberrations. Cardiac neutrophil infiltration subsequent release myeloperoxidase (MPO) leads the formation oxidant hypochlorous acid (HOCl) that able chemically modify plasmalogens (ether-phospholipids) abundantly present heart. This reaction gives rise reactive lipid species including aldehydes chlorinated fatty acids. During study, we tested...
Trophoblast invasion into uterine tissues represents a hallmark of first trimester placental development. As expression serum amyloid A4 (SAA4) occurs in tumorigenic and invasive we here investigated whether SAA4 is present trophoblast-like human AC1-M59/Jeg-3 cells trophoblast preparations term placenta. mRNA was expressed non-stimulated cytokine-treated cells. In purified upregulated at weeks 10 12 pregnancy. Western-blot immunohistochemical staining tissue revealed pronounced indicating...
Neutrophil-derived myeloperoxidase (MPO) and its potent oxidant, hypochlorous acid (HOCl), gained attention as important oxidative mediators in cardiac damage dysfunction. As cardiomyocytes generate low-density lipoprotein (LDL)-like particles, we aimed to identify the footprints of proatherogenic HOCl-LDL, which adversely affects cellular signalling cascades various cell types, human infarcted myocardium. We performed immunohistochemistry for MPO HOCl-LDL myocardial tissue, investigated...