A5077283478- Barrier Structure and Function Studies
- Electron Spin Resonance Studies
- Neurological Disease Mechanisms and Treatments
- Nitric Oxide and Endothelin Effects
- Inflammation biomarkers and pathways
- Connexins and lens biology
- Free Radicals and Antioxidants
- Immune cells in cancer
- Photosynthetic Processes and Mechanisms
- Redox biology and oxidative stress
- Advanced Proteomics Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Eicosanoids and Hypertension Pharmacology
- Sulfur Compounds in Biology
- S100 Proteins and Annexins
- Drug Transport and Resistance Mechanisms
- Analytical Chemistry and Sensors
- Biochemical effects in animals
- Cancer, Hypoxia, and Metabolism
- Mass Spectrometry Techniques and Applications
- Plant Stress Responses and Tolerance
- Gut microbiota and health
- Caveolin-1 and cellular processes
- Mitochondrial Function and Pathology
- bioluminescence and chemiluminescence research
Leibniz-Forschungsinstitut für Molekulare Pharmakologie
2012-2024
Leibniz Association
1997-2022
Leibniz Institute for Neurobiology
2006-2007
Institute for Biological Sciences
2006
Humboldt-Universität zu Berlin
1997-2005
Institute of Chemical Kinetics and Combustion
1998
Novosibirsk Institute of Organic Chemistry
1998
Charité - Universitätsmedizin Berlin
1997
Physikalisch-Technische Bundesanstalt
1992
Institute of Pharmacology
1992
The outcome of stroke is greatly influenced by the state blood–brain barrier (BBB). BBB endothelium sealed paracellularly tight junction (TJ) proteins, i.e., claudins (Cldns) and redox regulator occludin. Functions Cldn3 occludin at are largely unknown, particularly after stroke. We address effects deficiency stress factors on its TJs. tightened for small molecules ions, limited endothelial endocytosis, strengthened TJ structure controlled Cldn1 expression. After middle cerebral artery...
This review addresses the role of tight junction proteins at blood-brain barrier (BBB). Their expression is described, and their in physiological pathological processes BBB discussed. Based on this, new approaches are depicted for paracellular drug delivery diagnostics treatment cerebral diseases. Recent data provide convincing evidence that, addition to its impairment course diseases, could be involved aetiology CNS disorders. Further progress will expected based insights protein structure...
The blood–brain barrier (BBB) formed by the microvascular endothelium limits cerebral drug delivery. paraendothelial cleft is sealed tight junctions (TJs) with a major contribution from claudin‐5, which we selected as target to modulate BBB permeability. For this purpose, drug‐enhancer peptides were designed based on first extracellular loop (ECL) of claudin‐5 allow transient permeabilization. Peptidomimetics (C5C2 and derivatives, nanomolar affinity claudin‐5) size‐selectively (≤40 kDa)...
A cell culture model of blood‐brain barrier (BBB, coculture rat brain endothelial cells with astrocytes) was used to investigate the effect nitric oxide ( ⋅ NO) on damage BBB induced by hypoxia/reoxygenation (H/R). Permeability coefficient fluorescein across endothelium as a marker tightness. The permeability increased 5.2 times after H/R indicating strong disruption BBB. presence NO donor S ‐nitroso‐ N ‐acetylpenicillamine (SNAP, 30 μM), authentic (6 μM) or superoxide dismutase (50...
4-Hydroxynonenal (HNE) has been proposed as an important marker of radical-induced lipid peroxidation (LPO) during postischemic reperfusion injury the myocardium. Therefore, liberation HNE into effluent isolated perfused rat hearts was investigated. For first time, formation aldehyde is demonstrated in During control perfusion, 1.28 +/- 0.33 pmol HNE.min-1.mg protein-1 were formed by 18-mo-old Wistar-Kyoto (WKY) rats and 2.74 1.12 pmol.min-1.mg those spontaneously hypertensive (SHR) rats,...
The affinity of titanium dioxide for phosphate groups has been successfully used enrichment phosphopeptides from complex mixtures. This paper reports the relationship between occurrence some amino acids and phospho-specific nonspecific binding peptides that occurs during enrichment. In order to perform a systematic study, two well-characterized peptide mixtures consisting either 33 or 8 synthetic their nonphosphorylated analogs, which differed in charge hydrophobicity, were synthesized...
Tight junctions (TJs) seal paracellular clefts in epithelia/endothelia and form tissue barriers for proper organ function. TJ-associated marvel proteins (TAMPs; tricellulin, occludin, marvelD3) are thought to be relevant regulation. Under normal conditions, tricellulin tightens tricellular against macromolecules. Traces of occur bicellular junctions.As pathological disturbances have not been analyzed, the structure function human including potentially redox-sensitive Cys sites, were...
Cerebral ischemia causes functional alteration of the blood-brain barrier, formed by brain capillary endothelial cells (BCEC). Changes in protein expression and activity selected differentially expressed enzymes were investigated BCEC subjected to hypoxia (24 h) alone or followed a 24-h reoxygenation. proteins isolated, separated 2-DE, identified MALDI-MS. Computer-based 2-D gel analysis 21 up-regulated 4 down-regulated after 9 that further posthypoxic The majority hypoxia-induced was...
The paracellular cleft within epithelia/endothelia is sealed by tight junction (TJ) proteins. Their extracellular loops (ECLs) are assumed to control permeability and targets of pathogenes. We demonstrated that claudin-1 crucial for tightening. Its ECL1 essential the sealing contains two cysteines conserved throughout all claudins. Aims: prove hypothesis this cysteine motif forms a redox-sensitive intramolecular disulfide bridge and, hence, claudin-1-ECL1 constitutes functional structure...
Spin trapping compounds are used frequently to detect free radicals released by cells. Their cytotoxicity has be considered in order prevent perturbations of normal cell growth and viability. Eleven spin traps (eight nitrones three nitroso traps) have been tested for their effects on bovine aortic endothelial cells (toxicity range, 50% survival rate). The lowest was found 5,5‐dimethylpyrroline‐1‐oxide 2,2,4‐trimethyl‐2 H ‐imidazole‐1‐oxide whereas nitrosobenzene 2‐methyl‐2‐nitrosopropane...
The blood−brain barrier (BBB) is formed by endothelial cells of cerebral microvessels sealed tight junctions. Ischemic brain injury known to initiate a series biochemical and molecular processes that lead the disruption BBB, development vascular inflammation, subsequent neurovascular remodeling including angiogenesis. Molecular effectors these changes are multiple regulated in dynamic fashion. current study was designed analyze cellular secreted proteins rat (BEC) exposed ischemic insult...
Claudins (Cldns) are transmembrane tight junction (TJ) proteins that paracellularly seal endo- and epithelial barriers by their interactions within the TJs. However, mechanisms allowing TJ remodeling while maintaining barrier integrity largely unknown. Cldns occludin heterophilically homophilically cross-over endocytosed into neighboring cells in large, double membrane vesicles. Super-resolution microscopy confirmed presence of these vesicles revealed a distinct separation derived from...
Nitroxides are known to exert superoxide dismutase-mimetic properties and decrease O·̄<sub>2</sub>- H<sub>2</sub>O<sub>2</sub>-mediated cytotoxicity. However, the effect of nitroxides on <sup>⋅</sup>NO homeostasis has not been studied yet. The present study investigates detectable amount released by 3-morpholinosydnonimine (SIN-1) cultured endothelial cells. Cultured bovine aortic atrial cells stimulated with 10 μm A23187 a stable flux <sup>⋅</sup>NO, as detected chemiluminescence. Addition...