A5071949659- Platelet Disorders and Treatments
- Nitric Oxide and Endothelin Effects
- Antiplatelet Therapy and Cardiovascular Diseases
- Receptor Mechanisms and Signaling
- Phosphodiesterase function and regulation
- Erythrocyte Function and Pathophysiology
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Ion Transport and Channel Regulation
- Renin-Angiotensin System Studies
- Cell Adhesion Molecules Research
- Adenosine and Purinergic Signaling
- Blood properties and coagulation
- Diabetes Treatment and Management
- Protein Kinase Regulation and GTPase Signaling
- Eicosanoids and Hypertension Pharmacology
- Hormonal Regulation and Hypertension
- Drug Transport and Resistance Mechanisms
- Chemotherapy-induced organ toxicity mitigation
- Cardiac Ischemia and Reperfusion
- Cardiomyopathy and Myosin Studies
- Protease and Inhibitor Mechanisms
- Heart Failure Treatment and Management
- Ion channel regulation and function
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phytochemicals and Antioxidant Activities
Institute of Evolutionary Physiology and Biochemistry
2016-2025
St Petersburg University
2016-2022
University Medical Center of the Johannes Gutenberg University Mainz
2017-2021
Johannes Gutenberg University Mainz
2001-2021
University of Würzburg
2007-2016
Russian Academy of Sciences
2000-2014
Leibniz Institute for Analytical Sciences - ISAS
2014
Maastricht University
2014
University of Aberdeen
2014
Universitätsklinikum Würzburg
2012-2013
Vasodilator-stimulated phosphoprotein (VASP), a substrate of cAMP- and cGMP-dependent protein kinases, is associated with focal adhesions, cell–cell contacts, microfilaments, highly dynamic membrane regions. VASP, which expressed in most cell types particularly high levels human platelets, binds to profilin, zyxin, vinculin, F-actin, the Listeria monocytogenes surface ActA. VASP member enabled (Ena)/VASP family thought be involved actin filament formation integrin α IIb β 3 inhibition...
Beside their main physiological function in hemostasis, platelets are also highly involved pathological processes, such as atherothrombosis and inflammation. During binding of adhesive substrates to tyrosine-kinase-linked adhesion receptors and/or soluble agonists G-protein coupled leads a cascade intracellular signaling processes based on substrate (de)phosphorylation. The same mechanisms platelet activation at sites atherosclerotic plaque rupture, contributing vessel occlusion consequently...
Protein kinase A (PKA) activation by cAMP phosphorylates multiple target proteins in numerous platelet inhibitory pathways that have a very important role maintaining circulating platelets resting state. Here we show thrombin- and collagen-stimulated platelets, PKA is activated cAMP-independent mechanisms involving dissociation of the catalytic subunit (PKAc) from an NFκB-IκBα-PKAc complex. We demonstrate mRNA protein expression for most NFκB family members platelets. From PKAc was...
Previous research has suggested that cGMP-dependent protein kinases (cGKs) may play a role in long-term potentiation hippocampus, but their site of action been unknown. We examined this question at synapses between pairs hippocampal neurons dissociated cell culture. Injection specific peptide inhibitor cGK into the presynaptic not postsynaptic neuron blocked long-lasting induced by tetanic stimulation neuron. As controls, injection scrambled or cAMP-dependent kinase either did block...
NO acting through soluble guanylyl cyclase and cGMP formation is a negative regulator of cardiomyocyte hypertrophy. Downstream targets mediating the inhibitory effects NO/cGMP on hypertrophy have not been elucidated. In addition to its antihypertrophic effects, promotes apoptosis in cardiomyocytes, presumably cGMP-independent pathways. We investigated role cGMP-dependent protein kinase (PKG) proapoptotic NO. Incubation neonatal rat cardiomyocytes with donor S -nitroso- N -acetyl- d , l...
Cyclic nucleotide phosphodiesterases (PDEs) are the enzymes that catalyze hydrolysis of cAMP and cGMP, thereby restricting activity these second messengers in cells. A unique ability to shape gradients cyclic nucleotides compartmentalize their signaling implies a high potency rapid action PDEs. However, it has not been demonstrated how fast PDEs can hydrolyze living system. Here we perform real-time monitoring PDE2 aldosterone-producing adrenal cells using recently developed genetically...
Certain pathogenic bacteria produce a family of heat stable enterotoxins (STa) which activate intestinal guanylyl cyclases, increase cGMP, and elicit life-threatening secretory diarrhea. The intracellular effector cGMP actions has not been clarified. Recently we cloned the cDNA for rat type II dependent protein kinase (cGK II) is highly enriched in mucosa. Here show that cGK mRNA are restricted to segments from duodenum proximal colon, with highest amounts jejunum. decreased along villus...
Phosphodiesterase type 2A (PDE2A) hydrolyzes cyclic nucleotides cAMP and cGMP, thus efficiently controlling cNMP-dependent signaling pathways. PDE2A is composed of an amino-terminal region, two regulatory GAF domains, a catalytic domain. Cyclic nucleotide hydrolysis known to be activated by cGMP binding GAF-B; however, other mechanisms may operate fine-tune local levels. In yeast two-hybrid screening we identified XAP2, crucial component the aryl hydrocarbon receptor (AhR) complex, as major...
Cardiac atrial natriuretic peptide (ANP) and B-type (BNP) modulate blood pressure volume by activation of the receptor guanylyl cyclase-A (GC-A) subsequent intracellular cGMP formation. Here we report what believe to be a novel function these peptides as paracrine regulators vascular regeneration. In mice with systemic deletion GC-A gene, regeneration in response critical hind limb ischemia was severely impaired. Similar attenuation ischemic angiogenesis observed conditional, endothelial...
Extracellular vesicles (EVs) released by different cell types play an important role in many physiological and pathophysiological processes. In conditions, red blood (RBC)-derived EVs compose 4-8% of all circulating EVs, oxidative stress (OS) as a consequence conditions significantly increases the amount circulated RBC-derived EVs. However, mechanisms EV formation are not yet fully defined. To analyze OS-induced RBC transformations, we used flow cytometry to evaluate esterase activity,...
Hemolysis during severe diseases (malaria, hemorrhagic stroke, sickle cell disease, etc.) and blood transfusion induces the release of free hemoglobin, which degrades to highly reactive toxic compounds—hemin hematin. Oxidized heme derivatives induce platelet activation, aggregation, degranulation, leading prothrombotic inflammatory events. In present study, we showed that hematin is a more potent agonist activation than hemin, using several methods, including original laser diffraction...
Abstract: In brains of the rabbit, pig, and human, expression high‐affinity Na + ‐ d ‐glucose cotransporter SGLT1 protein RS1, which alters activity SGLT1, was demonstrated. situ hybridization showed that RS1 are transcribed in pyramidal cells brain cortex hippocampus Purkinje cerebellum. neurons pig demonstrated by western blotting with synaptosomal membranes immunohistochemistry, cells. To test whether may be activated during increased consumption, an epileptic seizure induced rat brain,...
Many signal transduction pathways are mediated by the second messengers cGMP and cAMP, cGMP- cAMP-dependent protein kinases (cGK PKA), phosphodiesterases, ion channels. To distinguish among different effectors, inhibitors of cGK PKA have been developed including K-252 compound KT5823 isoquinolinesulfonamide H89. KT5823, an <i>in vitro</i> inhibitor cGK, has also used in numerous studies with intact cells to implicate or rule out involvement this kinase a given cellular response. However,...
Spatial and temporal regulation of intracellular Ca<sup>2+</sup> is a key event in many signaling pathways. Plasma membrane Ca<sup>2+</sup>-ATPases (PMCAs) are major regulators homeostasis bind to PDZ (PSD-95/Dlg/ZO-1) domains via their C termini. Various membrane-associated guanylate kinase family members have been identified as interaction partners PMCAs. In particular, SAP90/PSD95, PSD93/chapsyn-110, SAP97, SAP102 all the C-terminal tails PMCA "b" splice variants. Additionally, it has...