55 results on '"Jutta Meyer"'
Search Results
2. Light Adaptation of Rod Photoreceptor Synapses by a Transducin-Complexin-SNARE Complex Interaction
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Uwe Thorsten Lux, Jutta Meyer, Olaf Jahn, Adam Davison, Norbert Babai, Andreas Gießl, Anna Wartenberg, Heinrich Sticht, Nils Brose, Kerstin Reim, and Johann Helmut Brandstätter
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History ,Polymers and Plastics ,Business and International Management ,Industrial and Manufacturing Engineering - Published
- 2023
3. BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor
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Daniel Meibom, Sina Micus, Anna Lena Andreevski, Sonja Anlauf, Pamela Bogner, Clemens-Jeremias von Buehler, André P. Dieskau, Jan Dreher, Frank Eitner, Daniela Fliegner, Markus Follmann, Kersten Matthias Gericke, Stefanie Maassen, Jutta Meyer, Karl-Heinz Schlemmer, Holger Steuber, Adrian Tersteegen, and Frank Wunder
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Heart Failure ,Mice ,3',5'-Cyclic-AMP Phosphodiesterases ,Drug Discovery ,Molecular Medicine ,Animals ,Cyclic GMP ,High-Throughput Screening Assays - Abstract
Despite advances in the treatment of heart failure in recent years, options for patients are still limited and the disease is associated with considerable morbidity and mortality. Modulating cyclic guanosine monophosphate levels within the natriuretic peptide signaling pathway by inhibiting PDE9A has been associated with beneficial effects in preclinical heart failure models. We herein report the identification of BAY-7081, a potent, selective, and orally bioavailable PDE9A inhibitor with very good aqueous solubility starting from a high-throughput screening hit. Key aspect of the optimization was a switch in metabolism of our lead structures from glucuronidation to oxidation. The switch proved being essential for the identification of compounds with improved pharmacokinetic profiles. By studying a tool compound in a transverse aortic constriction mouse model, we were able to substantiate the relevance of PDE9A inhibition in heart diseases.
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- 2022
4. Urinary miRNA Profiles in Chronic Kidney Injury-Benefits of Extracellular Vesicle Enrichment and miRNAs as Potential Biomarkers for Renal Fibrosis, Glomerular Injury, and Endothelial Dysfunction
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Barbara Petzuch, Agnès Bénardeau, Lucas Hofmeister, Jutta Meyer, Elke Hartmann, Mira Pavkovic, Ilka Mathar, Peter Sandner, and Heidrun Ellinger-Ziegelbauer
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Male ,Toxicology ,Kidney ,Fibrosis ,Rats ,Extracellular Vesicles ,MicroRNAs ,Hypertension ,Renin ,Disease Progression ,Animals ,Humans ,Female ,Obesity ,Renal Insufficiency, Chronic ,Biomarkers - Abstract
Micro-RNAs (miRNAs) are regulators of gene expression and play an important role in physiological homeostasis and disease. In biofluids, miRNAs can be found in protein complexes or in extracellular vesicles (EVs). Altered urinary miRNAs are reported as potential biomarkers for chronic kidney disease (CKD). In this context, we compared established urinary protein biomarkers for kidney injury with urinary miRNA profiles in obese ZSF1 and hypertensive renin transgenic rats. Additionally, the benefit of urinary EV enrichment was investigated in vivo and the potential association of urinary miRNAs with renal fibrosis in vitro. Kidney damage in both rat models was confirmed by histopathology, proteinuria, and increased levels of urinary protein biomarkers. In total, 290 miRNAs were elevated in obese ZSF1 rats compared with lean controls, whereas 38 miRNAs were altered in obese ZSF1 rats during 14–26 weeks of age. These 38 miRNAs correlated better with disease progression than established urinary protein biomarkers. MiRNAs increased in obese ZSF1 rats were associated with renal inflammation, fibrosis, and glomerular injury. Eight miRNAs were also changed in urinary EVs of renin transgenic rats, including one which might play a role in endothelial dysfunction. EV enrichment increased the number and detection level of several miRNAs implicated in renal fibrosis in vitro and in vivo. Our results show the benefit of EV enrichment for miRNA detection and the potential of total urine and urinary EV-associated miRNAs as biomarkers of altered kidney physiology, renal fibrosis and glomerular injury, and disease progression in hypertension and obesity-induced CKD.
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- 2022
5. Runcaciguat, a novel soluble guanylate cyclase activator, shows renoprotection in hypertensive, diabetic, and metabolic preclinical models of chronic kidney disease
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Peter Sandner, Johannes-Peter Stasch, Bettina Lawrenz, Joerg Hueser, Mira Pavkovic, Frank Eitner, Elke Hartmann, Jutta Meyer, Antje Kahnert, Tibor Schomber, Agnès Bénardeau, Ilka Mathar, Axel Kretschmer, Michael G. Hahn, and Jan R. Kraehling
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Male ,Cyclopropanes ,Time Factors ,Enzyme Activators ,Blood Pressure ,Pharmacology ,medicine.disease_cause ,sGC activator ,Nitric oxide ,Diabetes Mellitus, Experimental ,Runcaciguat ,Rats, Sprague-Dawley ,DKD ,chemistry.chemical_compound ,Soluble Guanylyl Cyclase ,Renin–angiotensin system ,CKD ,Medicine ,Animals ,Renal Insufficiency, Chronic ,Cyclic guanosine monophosphate ,Cyclic GMP ,Kidney ,Dose-Response Relationship, Drug ,business.industry ,General Medicine ,medicine.disease ,Rats ,Rats, Zucker ,cGMP ,Disease Models, Animal ,medicine.anatomical_structure ,Blood pressure ,chemistry ,Hypertension ,Original Article ,Rats, Transgenic ,business ,Soluble guanylyl cyclase ,Oxidative stress ,Kidney disease - Abstract
Graphical abstract Chronic kidney diseaQueryse (CKD) is associated with oxidative stress which can interrupt the nitric oxide (NO)/soluble guanylyl cyclase (sGC) signaling and decrease cyclic guanosine monophosphate (cGMP) production. Low cGMP concentrations can cause kidney damage and progression of CKD. The novel sGC activator runcaciguat targets the oxidized and heme-free form of sGC, restoring cGMP production under oxidative stress. The purpose of this study is to investigate if runcaciguat could provide an effective treatment for CKD. Runcaciguat was used for the treatment not only in rat CKD models with different etiologies and comorbidities, namely of hypertensive rats, the renin transgenic (RenTG) rat, and angiotensin-supplemented (ANG-SD) rat, but also in rats with diabetic and metabolic CKD, the Zucker diabetic fatty (ZDF) rat. The treatment duration was 2 to 42 weeks and runcaciguat was applied orally in doses from 1 to 10 mg/kg/bid. In these different rat CKD models, runcaciguat significantly reduced proteinuria (urinary protein to creatinine ratio; uPCR). These effects were also significant at doses which did not or only moderately decrease systemic blood pressure. Moreover, runcaciguat significantly decreased kidney injury biomarkers and attenuated morphological kidney damages. In RenTG rats, runcaciguat improved survival rates and markers of heart injury. These data demonstrate that the sGC activator runcaciguat exhibits cardio-renal protection at doses which did not reduce blood pressure and was effective in hypertensive as well as diabetic and metabolic CKD models. These data, therefore, suggest that runcaciguat, with its specific mode of action, represents an efficient treatment approach for CKD and associated CV diseases. Supplementary Information The online version contains supplementary material available at 10.1007/s00210-021-02149-4.
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- 2021
6. Submerged vegetation in a shallow brackish lagoon does not enhance water clarity but offers substantial refuge for zooplankton
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Irmgard Blindow, Milena Kafka, Božena L. Nawka, Caroline Lindner, Sven Dahlke, Jutta Meyer, Sandra Kube, Rhena Schumann, Antje Kerkow, and Hendrik Schubert
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0106 biological sciences ,Abiotic component ,Hydrology ,Brackish water ,010604 marine biology & hydrobiology ,Plant Science ,Aquatic Science ,010603 evolutionary biology ,01 natural sciences ,Zooplankton ,Water clarity ,medicine ,Environmental science ,medicine.symptom ,Water transparency ,Vegetation (pathology) - Abstract
The small-scale impact of submerged vegetation (locally enhanced water transparency) on abiotic / biotic parameters was studied in a shallow (
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- 2019
7. Sedimentation in a shallow brackish water lagoon influenced by wind-induced waves - A methodical study
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Vivien Leonhardt, Jutta Meyer, and Irmgard Blindow
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0106 biological sciences ,010504 meteorology & atmospheric sciences ,Brackish water ,Water Movements ,010604 marine biology & hydrobiology ,Aquatic ecosystem ,Sediment ,Soil science ,Aquatic Science ,Sedimentation ,Oceanography ,01 natural sciences ,Water depth ,Water column ,Environmental science ,Ecosystem ,0105 earth and related environmental sciences - Abstract
In shallow aquatic ecosystems, wave-induced water motions affect the whole water column down to the sediment. To estimate the influence of these motions on short-term sedimentation rates (SR) in a shallow wind-exposed lagoon, we used plate traps (PTs) which, in contrast to cylindrical traps (CTs), allow trapped matter to become resuspended. In a series of experiments, we varied distance to the sediments, water depth, incubation time, and studied the SRs of total suspended matter and of suspended organic matter at varying conditions of wave exposure. The coefficient of variation of SRs did not change with incubation time. While SRs were similar on both trap types at very low wave exposure, they decreased with increasing wave exposure on the PTs probably due to instantaneous resuspension. In the CTs, SRs increased with increasing wave exposure. This resulted in about 55 times higher SRs in the CTs than on the PTs at high wave exposure. We conclude that CTs are not suitable to estimate natural SRs in wave-affected waters as they overestimate SRs. Our results indicate that SR obtained by PTs, which were here used for the first time in a wind-exposed, non-tidal ecosystem, are a far better estimate for natural short-term SRs.
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- 2019
8. Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix
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Divya Sachidanandan, Steffen Altrichter, Nadine Ehmann, Kerstin Reim, Nicole Scholz, Cordelia Imig, Robert J. Kittel, Olaf Jahn, Jutta Meyer, Marius Lamberty, Manfred Heckmann, Martin Pauli, Nils Brose, Benjamin H. Cooper, Anne Bormann, Stefan Hallermann, Christian Stigloher, and Tobias Langenhan
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Nerve Tissue Proteins ,Neurotransmission ,Biology ,Synaptic vesicle ,Article ,Exocytosis ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Protein Domains ,Complexin ,Animals ,Drosophila Proteins ,Active zone ,Neurotransmitter ,Research Articles ,Adaptor Proteins, Signal Transducing ,030304 developmental biology ,SNARE complex assembly ,Mice, Knockout ,0303 health sciences ,Neuronal Plasticity ,Cell Biology ,Cell biology ,Adaptor Proteins, Vesicular Transport ,Drosophila melanogaster ,chemistry ,Synaptic Vesicles ,SNARE Proteins ,030217 neurology & neurosurgery ,Presynaptic active zone - Abstract
By performing an in vivo screen in Drosophila melanogaster, Scholz, Ehmann, et al. identify Complexin as a functional interaction partner of Bruchpilot. The two proteins mediate a physical attachment of synaptic vesicles to the active zone cytomatrix and promote rapid, sustained synaptic transmission., Information processing by the nervous system depends on neurotransmitter release from synaptic vesicles (SVs) at the presynaptic active zone. Molecular components of the cytomatrix at the active zone (CAZ) regulate the final stages of the SV cycle preceding exocytosis and thereby shape the efficacy and plasticity of synaptic transmission. Part of this regulation is reflected by a physical association of SVs with filamentous CAZ structures via largely unknown protein interactions. The very C-terminal region of Bruchpilot (Brp), a key component of the Drosophila melanogaster CAZ, participates in SV tethering. Here, we identify the conserved SNARE regulator Complexin (Cpx) in an in vivo screen for molecules that link the Brp C terminus to SVs. Brp and Cpx interact genetically and functionally. Both proteins promote SV recruitment to the Drosophila CAZ and counteract short-term synaptic depression. Analyzing SV tethering to active zone ribbons of cpx3 knockout mice supports an evolutionarily conserved role of Cpx upstream of SNARE complex assembly.
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- 2019
9. Long-term and interannual changes of submerged macrophytes and their associated diaspore reservoir in a shallow southern Baltic Sea bay: influence of eutrophication and climate
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Marko Hendreschke, Jutta Meyer, Antje Kerkow, Irmgard Blindow, Sven Dahlke, Annika Dewart, and Sandra Flügge
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0106 biological sciences ,Ruppia ,Chara ,Diaspore (botany) ,biology ,Ecology ,010604 marine biology & hydrobiology ,Vegetation ,Aquatic Science ,biology.organism_classification ,010603 evolutionary biology ,01 natural sciences ,Macrophyte ,Potamogeton ,Eutrophication ,Bay - Abstract
Long-term and interannual changes in composition of submerged vegetation, diaspore reservoir and germination were investigated in the lagoon system Westrugensche Boddenkette, Baltic Sea, north-east Germany. Comparison with a survey from 1932, showed vegetation cover is similar to the past, maintaining high cover to depths of 2.8 m despite a period of eutrophication between about 1960 and 1990. Species dominance shifted, however, from small charophytes to larger species like Potamogeton pectinatus. We explain interannual vegetation changes by weather conditions. Such changes were observed in several species, most notably in Chara canescens. This annual species seems to be favoured by extensive winter ice cover. The diaspore reservoir and the germination success of submerged macrophytes do not mirror their frequency in the vegetation, but rather reflect life form strategies. Small oospores, mainly of annual charophytes, represented >97% of all diaspores but very few Chara oospores germinated. The numerous Tolypella oospores probably originated from a discrete period with high abundance during the 1950s and have completely failed to germinate. Angiosperm seeds are larger and less frequent but have higher germination success, especially Ruppia seeds. In conclusion, charophytes are outcompeted by larger angiosperms due to the combined effect of moderate eutrophication and climate change.
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- 2016
10. Overexpression of prostaglandin EP3 receptors activates calcineurin and promotes hypertrophy in the murine heart
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Jutta Meyer-Kirchrath, Thomas Hohlfeld, Christina Schooss, Jürgen Schrader, Ulrich Flögel, Jens W. Fischer, Andrea Marzoll, Karsten Schrör, Melanie Martin, and Christoph Jacoby
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medicine.medical_specialty ,Physiology ,Decorin ,Prostaglandin ,Cardiomegaly ,GTP-Binding Protein alpha Subunits, Gi-Go ,Ventricular Function, Left ,Muscle hypertrophy ,Mice ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,Cyclic AMP ,medicine ,Animals ,Receptors, Prostaglandin E ,Myocytes, Cardiac ,Transgenes ,Prostaglandin E2 ,Ventricular Remodeling ,biology ,Calcineurin ,Biglycan ,NFAT ,Magnetic Resonance Imaging ,Endocrinology ,chemistry ,Receptors, Prostaglandin E, EP3 Subtype ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Creatine kinase ,Cardiology and Cardiovascular Medicine ,Signal Transduction ,medicine.drug - Abstract
Aims Prostaglandin E2 (PGE2) has been shown to mediate anti-ischaemic effects and cardiomyocyte hypertrophy and there is evidence for an involvement of the prostaglandin EP3-receptor subtype. This study focuses on the EP3-mediated hypertrophic action and investigates intracellular signalling pathways of the EP3-receptor subtype in the murine heart. Methods and results Cardiac function was analyzed in vivo by magnetic resonance imaging (MRI) in transgenic (tg) mice with cardio-specific overexpression of the EP3 receptor in comparison with wild-type (wt) mice. Left ventricular (LV) function was determined in isolated perfused hearts subjected to 60 min of zero-flow ischaemia and 45 min of reperfusion. Calcineurin activity and nuclear activity of nuclear factor of activated T-cells (NFAT) were determined by a modified malachite green assay and ELISA, respectively. Extracellular matrix compounds were analyzed by RT–PCR and histology. MRI indicated a significant increase in end-diastolic and end-systolic volume in tg hearts. LV ejection fraction was severely decreased in tg hearts while the relative LV mass was significantly increased. In Langendorff perfused hearts, EP3-receptor overexpression resulted in a marked blunting of the ischaemia-induced increase in LV end-diastolic pressure and creatine kinase release. Analysis of EP3-receptor-mediated signalling revealed significantly increased calcineurin activity and nuclear activity of NFAT in tg hearts. Moreover, elevated mRNA levels of collagen types I and III as well as the collagen-binding proteoglycans biglycan and decorin were detected in tg hearts. Conclusion EP3-receptor-mediated signalling results in a significant anti-ischaemic action and activation of the pro-hypertrophic calcineurin signalling pathway, suggesting the involvement of the EP3 subtype in both PGE2-mediated cardioprotection as well as cardiac hypertrophy.
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- 2008
11. Selective Cyclooxygenase-2 Inhibition Upregulates Renal Cortical αv Integrin Expression
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Jutta Meyer-Kirchrath, Bernd Grabensee, Gunhild Heise, Karsten Schrör, Christoph Waldner, and Peter Heering
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medicine.medical_specialty ,Kidney ,Endothelium ,Physiology ,Integrin ,Inflammation ,General Medicine ,Biology ,urologic and male genital diseases ,Extracellular matrix ,medicine.anatomical_structure ,Endocrinology ,Downregulation and upregulation ,Nephrology ,Internal medicine ,Genetics ,medicine ,biology.protein ,Cyclooxygenase ,medicine.symptom ,Cell adhesion - Abstract
Background: Cyclooxygenase-2 (COX-2), the inducible isoform of the cyclooxygenases, is upregulated in various inflammatory renal diseases and responsible for prostaglandin formation. As prostaglandins are known to influence cell adhesion processes, we investigated the effect of COX-2 inhibition on the expression of αv integrins, which are also enhanced in renal diseases and control the adherence between the endothelium and the extracellular matrix (ECM) in the glomerulus. Methods: Healthy female Wistar rats and animals with previously induced passive Heymann nephritis (PHN) received either 5 mg/kg body weight/day celecoxib or a placebo. After 28 days, renal cortical mRNA expression of COX-2 and αv integrin subunits was determined. Results: Rats with PHN showed a significant 1.7-fold increase in renal cortical mRNA expression of αv integrin subunits. Treatment with celecoxib increased cortical αv integrin mRNA expression 2.2-fold (p < 0.05) in healthy animals and 4.0-fold (p < 0.05) in rats with PHN, but lowered COX-2 mRNA expression in rats with PHN to 0.8-fold (p < 0.05). An inverse correlation between the expression of COX-2 and αv integrins in rats with PHN was demonstrated. Conclusions: It is suggested that COX-2-derived prostaglandins suppress the expression of αv integrins. This implies a previously unknown role for COX-2 in chronic inflammation in the kidney.
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- 2004
12. Gene expression profile of the Gs-coupled prostacyclin receptor in human vascular smooth muscle cells
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Jutta Meyer-Kirchrath, Svenja Debey, Karsten Schrör, Christian Glandorff, and Lutz Kirchrath
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medicine.medical_specialty ,Time Factors ,Vascular smooth muscle ,Arteriosclerosis ,Gene Expression ,Prostacyclin ,Biology ,Receptors, Epoprostenol ,Hyaluronan Synthase 2 ,Biochemistry ,Muscle, Smooth, Vascular ,chemistry.chemical_compound ,Internal medicine ,Gene expression ,Cyclic AMP ,GTP-Binding Protein alpha Subunits, Gs ,medicine ,Humans ,Iloprost ,Prostacyclin receptor ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis ,Pharmacology ,Zinc finger transcription factor ,Gene Expression Profiling ,Epoprostenol ,Cell biology ,Vascular endothelial growth factor ,Endocrinology ,chemistry ,biology.protein ,Cyclooxygenase ,medicine.drug - Abstract
Migration and proliferation of medial smooth muscle cells (SMC) in the arterial intima contributes to the development of atherosclerotic plaques and restenotic processes after coronary angioplasty. Prostacyclin (PGI 2 )-mediated stimulation of cyclic adenosine 3′5′-monophosphate (cAMP) signaling is believed to be important for maintaining SMC in a quiescent state. In order to identify new cellular targets of PGI 2 /cAMP action, we have used microarray screening to examine changes in the transcriptional profile in human vascular SMC in response to exposure to the stable PGI 2 mimetic iloprost. We have identified 83 genes with significantly altered expression after iloprost (100 nM) exposure for 6 hr. Fifty-one genes were upregulated, among them stanniocalcin precursor (18.8±2.7), zinc finger transcription factor (7.8±2.0), hyaluronan synthase 2 (6.8±1.8), cyclooxygenase 2 (4.7±0.8), dual specific phosphatase (3.9±0.5) and vascular endothelial growth factor (2.3±0.4). Thirty-two genes were reduced, among them cystein-rich angiogenic protein (−14.9±1.3), monocyte chemotactic protein 1 (−7.4±1.1) and plasminogen activator inhibitor PAI-1 (−4.5±0.5). By means of semi-quantitative RT-PCR, time-courses of gene expression were established. The present study identified genes not hitherto recognized to be targets of PGI 2 action, providing further insight into its cAMP-mediated effects on SMC growth, migration and matrix secretion.
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- 2004
13. The Small RNA Profile during Drosophila melanogaster Development
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Thomas Tuschl, Alexei A. Aravin, Abdullah Yalcin, Terry Gaasterland, Jutta Meyer, Mariana Lagos-Quintana, Ben Snyder, Mihaela Zavolan, and Debora S. Marks
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Male ,Small RNA ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Testis ,Animals ,RasiRNA ,Cloning, Molecular ,RNA, Small Interfering ,Small nucleolar RNA ,Molecular Biology ,Gene Library ,Genetics ,Base Sequence ,Gene Expression Profiling ,Gene Expression Regulation, Developmental ,RNA ,Cell Biology ,Non-coding RNA ,Long non-coding RNA ,Chromatin ,MicroRNAs ,RNA silencing ,Drosophila melanogaster ,Developmental Biology - Abstract
Small RNAs ranging in size between 20 and 30 nucleotides are involved in different types of regulation of gene expression including mRNA degradation, translational repression, and chromatin modification. Here we describe the small RNA profile of Drosophila melanogaster as a function of development. We have cloned and sequenced over 4000 small RNAs, 560 of which have the characteristics of RNase III cleavage products. A nonredundant set of 62 miRNAs was identified. We also isolated 178 repeat-associated small interfering RNAs (rasiRNAs), which are cognate to transposable elements, satellite and microsatellite DNA, and Suppressor of Stellate repeats, suggesting that small RNAs participate in defining chromatin structure. rasiRNAs are most abundant in testes and early embryos, where regulation of transposon activity is critical and dramatic changes in heterochromatin structure occur.
- Published
- 2003
14. Iloprost down-regulates the expression of the growth regulatory gene Cyr61 in human vascular smooth muscle cells
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Jutta Meyer-Kirchrath, Svenja Debey, Karsten Schrör, and Lutz Kirchrath
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Neointima ,medicine.medical_specialty ,Vascular smooth muscle ,Down-Regulation ,Prostacyclin ,Biology ,Muscle, Smooth, Vascular ,Immediate-Early Proteins ,Internal medicine ,medicine ,Humans ,Iloprost ,Cells, Cultured ,Regulator gene ,Pharmacology ,Cell biology ,Vasoprotective ,Endocrinology ,medicine.anatomical_structure ,Gene Expression Regulation ,CYR61 ,cardiovascular system ,Intercellular Signaling Peptides and Proteins ,lipids (amino acids, peptides, and proteins) ,Cysteine-Rich Protein 61 ,medicine.drug ,Blood vessel - Abstract
Prostacyclin and its mimetics have repeatedly been shown to act antiatherogenic and to inhibit neointima formation in several animal models of vascular injury. Treatment of human vascular smooth muscle cells with the prostacyclin mimetic iloprost (100 nm) drastically reduces expression of Cyr61, encoding the growth-regulatory cystein-rich angiogenic protein, without affecting the degradation rate of Cyr61 mRNA. Thrombin-induced Cyr61 expression was inhibited completely in the presence of iloprost. It is concluded that vasoprotective actions of prostacyclin in vivo may in part be due to inhibition of expression of the growth regulatory gene Cyr61 at sites of vascular lesions.
- Published
- 2003
15. Long-term-desensitization of prostacyclin receptors is independent of the C-terminal tail
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Jutta Meyer-Kirchrath, Andreas Hasse, Sigrid M. Nilius, and Karsten Schrör
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Agonist ,medicine.drug_class ,medicine.medical_treatment ,media_common.quotation_subject ,Receptors, Prostaglandin ,Receptors, Cell Surface ,Prostacyclin ,Biology ,Receptors, Epoprostenol ,Transfection ,Biochemistry ,Homologous desensitization ,Cyclic AMP ,medicine ,Animals ,Humans ,Internalization ,Receptor ,Prostacyclin receptor ,Desensitization (medicine) ,media_common ,G protein-coupled receptor ,Pharmacology ,Epoprostenol ,Molecular biology ,Protein Structure, Tertiary ,COS Cells ,Sodium Fluoride ,medicine.drug - Abstract
Persistent stimulation of the Gs protein-coupled prostacyclin receptor (IP-R) causes its slow desensitization in a variety of cell types, a significant desensitization requiring several hours. To evaluate the role of the human IP-R C-terminus in desensitization and agonist-induced internalization, a C-terminally truncated hIP-receptor was generated. The C-terminal 68 amino acid residues were deleted by introduction of a stop codon for exchange of the original S319 codon (termed D318 mutant). Wild-type (WT) and truncated receptor were expressed in COS1 cells. Pretreatment of cells with the stable prostacyclin mimetic cicaprost (200 nM) desensitized cAMP production via WT and D318 receptors to similar extents. The cAMP response of WT and D318, respectively, was reduced by approximately 50% of maximal cAMP formation after 8 hr of continuous agonist stimulation, indicating significant long-term desensitization. Moreover, agonist-promoted sequestration of WT and D318 C-terminally tagged with green fluorescent protein was demonstrated, indicating that receptor internalization was not prevented by truncation of the C-terminus. These results demonstrated that long-term desensitization and sequestration of hIP-R did not depend on structures located in the hIP-R C-terminus.
- Published
- 2003
16. Regulation of cyclooxygenase-2 expression by iloprost in human vascular smooth muscle cells
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Svenja Debey, Karsten Schrör, and Jutta Meyer-Kirchrath
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Pharmacology ,medicine.medical_specialty ,Vascular smooth muscle ,Forskolin ,Prostanoid ,Prostacyclin ,Biology ,CREB ,Biochemistry ,Adenylyl cyclase ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,medicine ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Cyclooxygenase ,Iloprost ,medicine.drug - Abstract
Prostaglandin-endoperoxide synthase-2 (PGH-synthase) or cyclooxygenase-2 (COX-2) is inducible by a variety of stimuli, e.g. inflammatory mediators, growth factors and hormones and is believed to be responsible for the majority of inflammatory prostanoid production. Moreover, it has been demonstrated that COX-2 contributes substantially to prostacyclin-synthesis in patients with atherosclerosis. In this study, we demonstrate an up-regulation of COX-2 mRNA, protein and product formation by the prostacyclin-mimetic iloprost in human vascular smooth muscle cells (hSMC). COX-2 mRNA expression was induced transiently between 1 and 6 hr and returned to basal levels after 16 hr of iloprost stimulation. COX-2 protein was induced concomitantly between 3 and 6 hr of iloprost stimulation. This was accompanied by an increase in PGI 2 formation. Forskolin, a direct activator of adenylyl cyclase, and dibutyryl cAMP, a cell-permeable cAMP analogue-induced COX-2 mRNA, suggesting a cAMP-dependent COX-2 expression in hSMC. Iloprost-induced COX-2 protein expression and PGI 2 formation was synergistically elevated by co-stimulation with the phorbolester PMA (phorbol-12-myristate-13-acetate). It is concluded, that the observed up-regulation of COX-2 with subsequent release of newly synthesized PGI 2 and the synergistic effect of iloprost and phorbolester on PGI 2 formation provide a positive feedback of prostaglandins on their own synthesizing enzyme. This might be important for control of hSMC proliferation, migration and differentiation as well as inhibition of platelet aggregation.
- Published
- 2003
17. Obligatory Role of Cyclic Adenosine Monophosphate Response Element in Cyclooxygenase-2 Promoter Induction and Feedback Regulation by Inflammatory Mediators
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Ying Zhu, Xiao-Ming Xu, Jutta Meyer-Kirchrath, Michael A. Saunders, Wu Guo Deng, Karsten Schroer, and Kenneth K. Wu
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Transcriptional Activation ,medicine.medical_specialty ,Response element ,Inflammation ,Biology ,Response Elements ,Proinflammatory cytokine ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,Enhancer binding ,Cyclic AMP ,medicine ,Humans ,Cyclic adenosine monophosphate ,Promoter Regions, Genetic ,Cells, Cultured ,Cell Line, Transformed ,Tumor Necrosis Factor-alpha ,Membrane Proteins ,Nuclear Proteins ,Activating Transcription Factor 4 ,Chromatin ,Up-Regulation ,Cell biology ,Isoenzymes ,Endocrinology ,chemistry ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Cell culture ,Enzyme Induction ,Prostaglandins ,Trans-Activators ,Phorbol ,Tetradecanoylphorbol Acetate ,Tumor necrosis factor alpha ,Endothelium, Vascular ,Inflammation Mediators ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Interleukin-1 ,Transcription Factors - Abstract
Background — Cyclooxygenase-2 (COX-2) plays a key role in human inflammatory disorders such as vascular inflammation. COX-2 promoter activity is induced by proinflammatory mediators, but the role of cyclic adenosine monophosphate response element (CRE) in promoter stimulation remains unclear. Methods and Results — Transient transfection of a 0.9-kb COX-2 promoter fragment bearing CRE mutation abrogated COX-2 promoter activity induced by proinflammatory mediators in human endothelial cells and fibroblasts. Dual mutations of CRE and an upstream CCAAT/enhancer binding protein (C/EBP) site did not have an additional effect. Binding of CREB-2, ATF-2, USF-2, and c-Jun transactivators to a wild-type and CRE-mutated oligonucleotide was analyzed by a novel DNA-binding assay. CREB-2 and ATF-2 in nuclear extracts of unstimulated endothelial cells bound to CRE, whereas USF-2 and c-Jun or c-Fos bound to non-CRE sites. CREB-2 and c-Fos binding was increased by phorbol 12-myristate 13-acetate but not tumor necrosis factor-α. The binding assay and chromatin immunoprecipitation revealed binding of P300 coactivator to the COX-2 promoter region. Conclusions — CRE plays an obligatory role in COX-2 promoter activation by diverse stimuli. CREB-2 and ATF-2 bound to CRE serve as an anchor for P300 interaction with upstream transactivators and downstream transcription machinery.
- Published
- 2002
18. Cicatricial pemphigoid differs from bullous pemphigoid and pemphigoid gestationis regarding the fine specificity of autoantibodies to the BP180 NC16A domain
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Arno Kromminga, Jutta Meyer, Eva-B. Bröcker, Enno Schmidt, Enno Christophers, Cassian Sitaru, Detlef Zillikens, and Rüdiger Arndt
- Subjects
Pemphigoid ,DNA, Complementary ,Pemphigoid, Benign Mucous Membrane ,Dermatology ,Autoantigens ,Biochemistry ,Epitope ,Antibody Specificity ,Pregnancy ,Pemphigoid Gestationis ,Pemphigoid, Bullous ,medicine ,Humans ,Cicatricial pemphigoid ,Molecular Biology ,Autoantibodies ,Dermoepidermal junction ,integumentary system ,biology ,Chemistry ,Lichen Planus ,Autoantibody ,Non-Fibrillar Collagens ,medicine.disease ,Protein Structure, Tertiary ,Immunology ,biology.protein ,Female ,Bullous pemphigoid ,Antibody - Abstract
Bullous pemphigoid (BP), pemphigoid (herpes) gestationis (PG), cicatricial pemphigoid (CP), and lichen planus pemphigoides (LPP) are autoimmune subepidermal bullous diseases that are characterized by circulating autoantibodies to the transmembrane hemidesmosomal protein BP180/type XVII collagen. Previous studies demonstrated that the majority of patients with BP, PG, and LPP show antibodies to an immunodominant, membrane-proximal non-collagenous domain (NC16A) on the extracellular portion of BP180. By the use of non-overlapping peptides of the NC16A domain, we previously demonstrated that autoantibodies from BP and PG patients mainly react with epitopes clustered within the N-terminus of this immunodominant site of BP180; antibodies from patients with LPP also recognized the C-terminal portion of NC16A. However, some of these results had been obtained indirectly by preadsorption studies. The aim of the present study was to analyze the fine specificity of IgG autoantibodies to NC16A in sera from patients with CP and to compare their reactivity with antibodies from BP, PG, and LPP patients using a series of new overlapping fragments covering the entire NC16A domain. We confirm that BP and PG sera mainly react with N-terminal epitopes of NC16A, whereas sera from patients with LPP also bind to C-terminal portions, of this domain. Interestingly, out of ten patients with CP, the sera of seven reacted with NC16A; within NC16A, these sera bound to both C-terminal fragments and an N-terminal epitope right next to the cell membrane. Our data demonstrate a heterogeneous binding pattern of autoantibodies to BP180 NC16A in patients with CP.
- Published
- 2002
19. Evaluation of the Clinical Microbiology Profile of Moxifloxacin
- Author
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Glenn S. Tillotson, Jutta Meyer, and Christina Krasemann
- Subjects
Microbiology (medical) ,medicine.drug_class ,Moxifloxacin ,Antibiotics ,Drug resistance ,Pharmacology ,Minimum inhibitory concentration ,Anti-Infective Agents ,Clarithromycin ,medicine ,Humans ,heterocyclic compounds ,Respiratory Tract Infections ,Antibacterial agent ,Aza Compounds ,business.industry ,Drug Resistance, Microbial ,biochemical phenomena, metabolism, and nutrition ,Amoxicillin ,bacterial infections and mycoses ,Penicillin ,Treatment Outcome ,Infectious Diseases ,Immunology ,Quinolines ,business ,Fluoroquinolones ,medicine.drug - Abstract
Moxifloxacin is a new broad-spectrum antibacterial agent for treatment of respiratory tract infection of pathogens, including the major pathogens isolated in respiratory tract infections. The pharmacokinetic and pharmacodynamic properties of moxifloxacin are: excellent bioavailability, long half-life, and superior tissue penetration. Consequently, the 90% minimum inhibitory concentration (MIC(90)) values exhibited by moxifloxacin are generally lower than the concentrations of moxifloxacin found in circulation and in pulmonary tissues after a standard 400-mg dose given for up to 30 h. The relationship between moxifloxacin MIC(90) values and clinical response was investigated. The results of 13 clinical trials, performed in 30 countries between 1997 and 1998 and comprising 2618 patients treated with moxifloxacin or a comparator drug, were reviewed. Overall, 94% clinical success and 95% bacterial eradication was observed with moxifloxacin. These results were equivalent or superior to results seen with the comparator drugs. Clinical response rates and bacterial eradication rates with moxifloxacin were not significantly affected by bacterial resistance to other antibiotics (i.e., penicillin, clarithromycin, or amoxicillin). The majority (89%-97%) of the different bacterial strains with MICs for moxifloxacin < or =2 mg/L were successfully eradicated. In conclusion, moxifloxacin has potent in vivo bactericidal activity, and pathogen sensitivity to moxifloxacin is in accordance with US Food and Drug Administration and European suggested breakpoint values.
- Published
- 2001
20. Preservation of Gi coupling of a chimeric EP3/I-type prostaglandin (IP) receptor
- Author
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Andreas Hasse, Jutta Meyer-Kirchrath, and Karsten Schrör
- Subjects
Recombinant Fusion Proteins ,Prostaglandin E2 receptor ,Molecular Sequence Data ,Receptors, Prostaglandin ,CHO Cells ,Biology ,Receptors, Epoprostenol ,Transfection ,Biochemistry ,Beta-1 adrenergic receptor ,GTP-Binding Proteins ,Cricetinae ,Cyclic AMP ,Enzyme-linked receptor ,Animals ,Humans ,Receptors, Prostaglandin E ,5-HT5A receptor ,Amino Acid Sequence ,Prostaglandin receptor ,Protease-activated receptor 2 ,Pharmacology ,Molecular biology ,Interleukin-21 receptor ,COS Cells ,Receptors, Prostaglandin E, EP3 Subtype ,Adenosine A2B receptor - Abstract
For the EP 3 subtype of prostaglandin E receptors, different C-terminal splice variants are known, which are coupled to distinct heterotrimeric GTP-binding proteins (G-proteins). To test the hypothesis that the C-terminal domain is essential for the G-protein-coupling specificity of the EP 3 receptor, we exchanged the carboxyl-terminal tail of a porcine G i -coupled EP 3 receptor isoform for the corresponding C-terminal part of a G s -coupled prostaglandin receptor. The porcine EP 3 receptor was truncated at a lysine (K 350 ) residue at the end of the seventh transmembrane region, representing the splicing site of the different EP 3 receptor isoforms. The wild-type C-terminus (37 amino acids) was substituted by the C-terminal tail (89 amino acids) of the human I-type prostaglandin receptor (hIP-R). The G-protein coupling of the resulting chimeric receptor protein was studied in transfected Chinese hamster ovary (CHO) cells. Stimulation of the chimeric receptor protein with the EP 3 receptor-specific agonist M&B 28.767 did not increase adenosine 3′,5′-cyclic monophosphate (cAMP) formation but did reduce the forskolin-stimulated cAMP formation, indicating G i coupling. Furthermore, the chimeric receptor did not show constitutive activity as demonstrated for the C-terminally truncated EP 3 receptor. Thus, coupling specificity of the EP 3 receptor is not exclusively mediated by the carboxyl-terminal tail, and constitutive activity of a C-terminally truncated EP 3 receptor can be suppressed by the hIP-R C-terminus.
- Published
- 1999
21. Analysis of a porcine EP3-receptor: cloning, expression and signal transduction
- Author
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Jutta Meyer-Kirchrath, Thomas Hohlfeld, Petra Kuger, and Karsten Schrör
- Subjects
Transcription, Genetic ,Swine ,Molecular Sequence Data ,Gene Expression ,E-box ,Regulatory Sequences, Nucleic Acid ,Biology ,Ligands ,Radioligand Assay ,Cyclic AMP ,Animals ,Receptors, Prostaglandin E ,Amino Acid Sequence ,Cloning, Molecular ,Binding site ,Receptor ,Peptide sequence ,Transcription factor ,Pharmacology ,Base Sequence ,Sequence Homology, Amino Acid ,cDNA library ,Chinese hamster ovary cell ,Colforsin ,DNA ,Sequence Analysis, DNA ,General Medicine ,Molecular biology ,COS Cells ,Receptors, Prostaglandin E, EP3 Subtype ,lipids (amino acids, peptides, and proteins) ,Signal transduction ,Protein Binding ,Signal Transduction - Abstract
A cDNA clone, encoding a complete porcine EP3 receptor, was isolated from a porcine heart cDNA library. The deduced amino acid sequence revealed a protein of 387 amino acid residues with an estimated molecular weight of 43 kD and strongest homology to the human EP3-II receptor (84% identity on protein level). Ligand binding studies with transfected COS-7 cells, expressing the porcine receptor, showed displacement of [3H]PGE1 with the EP3-specific agonist MB 28.767, the EP1/EP3-agonist sulprostone but not with the EP2-specific agonist butaprost. Stimulation of transfected CHO cells with MB 28.767 resulted in inhibition of forskolin-induced cAMP formation, suggesting coupling to an inhibitory G protein. Agonist-induced translocation of the transcription factor NFkappaB into the nucleus of transfected CHO cells was demonstrated by Western blot analysis, indicating that these EP3 receptors modulate NFkappaB-dependent cellular signal transduction. Analysis of the genomic organization identified the major transcription initiation site at about 160 bp upstream of the ATG start codon. The 800-bp 5' flanking region contains a variety of putative cis-acting regulatory elements, including binding sites for AP2, SP1 and MyoD (E-box). The present data will now allow further studies on EP3 receptor-mediated signal transduction and its regulation.
- Published
- 1998
22. The bovine thromboxane A2 receptor: molecular cloning, expression, and functional characterization
- Author
-
Stephanie Muck, Artus-Aron Weber, Karsten Schrör, and Jutta Meyer-Kirchrath
- Subjects
DNA, Complementary ,medicine.drug_class ,Molecular Sequence Data ,Receptors, Thromboxane ,Sequence Homology ,Biology ,Transfection ,Binding, Competitive ,Thromboxane receptor ,Adenylyl cyclase ,Radioligand Assay ,chemistry.chemical_compound ,Enzyme-linked receptor ,medicine ,Animals ,Humans ,5-HT5A receptor ,Amino Acid Sequence ,Cloning, Molecular ,Receptor ,Peptide sequence ,Gene Library ,Pharmacology ,Base Sequence ,General Medicine ,Bridged Bicyclo Compounds, Heterocyclic ,Receptor antagonist ,Molecular biology ,Hydrazines ,chemistry ,Biochemistry ,15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid ,COS Cells ,Fatty Acids, Unsaturated ,Prostaglandins ,Endothelium, Vascular ,Signal transduction ,Adenylyl Cyclases - Abstract
This study describes the molecular cloning and functional characterization of the bovine thromboxane A2 (TP) receptor. Two partial nucleotide sequences coding for the bovine TP receptor were isolated from a bovine genomic and a bovine heart cDNA library. The deduced amino acid sequence suggests a heptahelical protein of 343 amino acids. The receptor protein is homologous with that of human placenta and endothelium at 84.0% and 81.4%, respectively. COS-7 cells were transfected with the bovine TP receptor cDNA, and binding affinities were assessed by radioligand binding studies. Specific displacement of [3H]SQ 29548 was demonstrated in COS-7 cell membranes with the unlabeled TP receptor antagonist SQ 29548 (Kd = 12.6+/-1.1 nM) and the TP receptor agonist U46619 (Kd = 192.1+/-58.9 nM), but not with other prostaglandins (PGD2, PGE1, PGF2alpha), or the PGI2 mimetic cicaprost. Agonist-induced stimulation of adenylyl cyclase in transfected COS-7 cells indicates a linkage to the cAMP signal transduction pathway via coupling to a stimulatory G-protein. Since bovine cells, e.g. vascular smooth muscle cells, are an established model to study the role of eicosanoids in cell signaling, this report on the molecular structure of the bovine TP receptor will allow further studies on receptor regulation.
- Published
- 1997
23. Expression, Function, and Regulation of E-Type Prostaglandin Receptors (EP 3 ) in the Nonischemic and Ischemic Pig Heart
- Author
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Jutta Meyer, Karsten Schrör, Thomas Hohlfeld, and Tom-Philipp Zucker
- Subjects
Male ,medicine.medical_specialty ,Swine ,Physiology ,Myocardial Ischemia ,Ischemia ,Prostaglandin ,Prostacyclin ,Biology ,Adenylyl cyclase ,Contractility ,chemistry.chemical_compound ,Sarcolemma ,Downregulation and upregulation ,Internal medicine ,medicine ,Animals ,Receptors, Prostaglandin E ,RNA, Messenger ,Alprostadil ,Receptor ,Prostaglandin E1 ,medicine.disease ,Endocrinology ,Gene Expression Regulation ,chemistry ,Female ,Cardiology and Cardiovascular Medicine ,medicine.drug - Abstract
Abstract The action of prostacyclin, prostaglandin E 1 (PGE 1 ), and their mimetics on myocardial function includes changes in contractility, electrophysiological properties, and protection from injury caused by transient myocardial ischemia. This study was undertaken to investigate the basic properties of myocardial E-type prostaglandin (EP) receptors. Ligand binding studies using an enriched preparation of sarcolemmal membranes prepared from pig hearts revealed a single class of binding sites for [ 3 H]PGE 1 , with a K d of 3.7 nmol/L and a B max of 92 fmol/mg protein. Competition experiments indicated highest affinity for EPs, suggesting an EP receptor. In addition, the EP receptor subtype–selective agonists sulprostone (EP 1 and EP 3 ) and M&B 28.767 (EP 3 ) were active, suggesting the presence of an EP 3 receptor subtype. PGE 1 stimulated sarcolemmal GTPase and inhibited sarcolemmal adenylyl cyclase activity, indicating EP 3 receptor coupling to an inhibitory G protein (G i ). Additional in vivo experiments showed that intracoronary infusion of PGE 1 (1 nmol/min) decreased isoprenaline-stimulated left ventricular contractile activity without altering systemic vascular resistance. This inhibition of β-adrenergic effects is compatible with the known myocardial anti-ischemic action of prostaglandins. Further experiments examined EP 3 receptor density and G-protein coupling in sarcolemma from ischemic and reperfused ischemic myocardium. In anesthetized open-chest minipigs, occlusion of the left anterior descending coronary artery for 60 minutes increased EP 3 receptor density by 50%, whereas receptor affinity was unchanged. This upregulation was prevented by pretreatment with colchicine (2 mg/kg IV), indicating microtubule-dependent receptor externalization. Northern hybridization showed comparable EP 3 receptor mRNA expression in control and ischemic myocardium. The increase of receptor protein was reversed during 60 minutes of reperfusion. G-protein coupling proved to be intact in ischemic and reperfused ischemic myocardial tissue, as shown by preserved GTP-γ-S–induced decrease of [ 3 H]PGE 1 binding. These data demonstrate for the first time that myocardial receptors for PGE 1 belong to the EP 3 subtype. The properties of this receptor include inhibition of adenylyl cyclase and upregulation during regional myocardial ischemia, suggesting an involvement in the anti-ischemic activity of E- and I-type prostaglandins.
- Published
- 1997
24. Cholesterol induces apoptosis-associated loss of the activated leukocyte cell adhesion molecule (ALCAM) in human monocytes
- Author
-
Jutta Meyer-Kirchrath, Anke C Rosenkranz, Andreas Böhm, Bernhard H. Rauch, Karsten Schrör, Thomas Hohlfeld, and Stefan J. Rauch
- Subjects
Apoptosis Inhibitor ,Physiology ,Vascular Cell Adhesion Molecule-1 ,Apoptosis ,Monocytes ,chemistry.chemical_compound ,Cell Movement ,Activated-Leukocyte Cell Adhesion Molecule ,Humans ,VCAM-1 ,Cell adhesion ,ALCAM ,Pharmacology ,ICAM-1 ,Membrane Glycoproteins ,U937 cell ,Dose-Response Relationship, Drug ,Cell adhesion molecule ,Chemistry ,Chemotaxis ,U937 Cells ,Atherosclerosis ,Flow Cytometry ,Intercellular Adhesion Molecule-1 ,Cell biology ,Cholesterol ,Gene Expression Regulation ,Molecular Medicine - Abstract
The activated leukocyte cell adhesion molecule (ALCAM/CD166) is associated with cell migration and leukocyte invasion into the vessel wall. This study investigates the impact of cholesterol loading on the expression of ALCAM, as compared with P-selectin glycoprotein ligand-1 (PSGL-1), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in monocytic U937 cells and human primary monocytes. Cells were enriched with cholesterol by incubation with a cyclodextrin-cholesterol complex. Expression of adhesion molecules and apoptosis was determined by flow cytometry. Migration was quantified by chemotaxis toward serum. Incubation with cholesterol (10-100 μg/ml) for 16 h caused a concentration-dependent increase in apoptosis. Enhanced apoptosis was associated with reduction of ALCAM by >70%. While PSGL-1 was affected similarly, expression of VCAM-1 was markedly increased by cholesterol and ICAM-1 levels were not regulated. The nonselective caspase/apoptosis inhibitor Q-VD-OPh partially prevented cholesterol-modulated alteration of adhesion molecule expression. Migration of cholesterol-rich monocytic cells toward serum was greatly reduced. This effect was partially restored by Q-VD-OPh and was dependent on ALCAM as shown by ALCAM-neutralizing antibodies. In conclusion, cholesterol-induced apoptosis in monocytes is accompanied by reduced expression of ALCAM and attenuated monocyte migration. This may restrain monocytes at cholesterol-rich sites and thereby expedite vascular lesion formation.
- Published
- 2010
25. Boson–fermion and baryon mapping: Construction of collective subspaces. I. Theory
- Author
-
Jutta Meyer
- Subjects
Condensed Matter::Quantum Gases ,Physics ,Particle physics ,Ideal (set theory) ,High Energy Physics::Lattice ,Quark model ,Statistical and Nonlinear Physics ,Fermion ,Quantum number ,Linear subspace ,Baryon ,Theoretical physics ,Mathematical Physics ,Subspace topology ,Boson - Abstract
Recently, the mathematical formalism of the Dyson boson mapping has been extended to a system of 3n fermions, leading to the boson–fermion and the baryon mapping. In the present paper, the case of a restriction to a subset of three‐fermion quantum numbers, the collective indices, is discussed. A theory is developed for the representation of fermionic states and operators in a truncated ideal space where only collective boson–fermion pairs or collective ideal baryons are allowed. An exact reproduction of physical properties is proved to be possible provided that the original fermionic problem can be solved in a subspace where all three‐fermion subsystems carry collective indices. Examples of simple applications are presented in the two subsequent papers of this series.
- Published
- 1992
26. Boson–fermion and baryon mapping: Construction of collective subspaces. II. Example: A simple quark shell model
- Author
-
Jutta Meyer
- Subjects
Quark ,Physics ,Particle physics ,Nuclear Theory ,High Energy Physics::Phenomenology ,Quark model ,Statistical and Nonlinear Physics ,Elementary particle ,Fermion ,Linear subspace ,Baryon ,Theoretical physics ,Nucleon ,Mathematical Physics ,Boson - Abstract
The formalism derived for the boson–fermion and the baryon mapping in Paper I of this series is applied to the single‐orbit quark shell model developed by Petry and co‐workers for the description of nuclear properties. The multiquark space is reduced to the collective subspace of multinucleon states. A collective representation of states and operators in terms of bosons and ideal fermions or in terms of ideal baryons, respectively, is constructed. The results of the original model in the multinucleon space are exactly reproduced. Finally, the two transformations are compared with a related mapping technique recently published by Pittel, Engel, Dukelsky, and Ring.
- Published
- 1992
27. Boson–fermion and baryon mapping: Construction of collective subspaces. III. Application of the baryon mapping to many‐baryon states
- Author
-
Jutta Meyer
- Subjects
Baryon ,Quark ,Physics ,Particle physics ,High Energy Physics::Phenomenology ,Statistical and Nonlinear Physics ,Fermion ,Invariant (mathematics) ,Space (mathematics) ,Quantum number ,Linear subspace ,Mathematical Physics ,Boson - Abstract
The theory developed in Paper I of this series is applied to the general case of a system consisting of colorfree quark triplets, whose quantum numbers are chosen as collective trifermion indices. The appropriate mapping technique to be used here is the baryon mapping. It is demonstrated that the original multiquark states can be exactly represented by states of colorfree ideal baryons. Besides, collective extended images are derived for a class of fermionic operators leaving the collective fermion space invariant.
- Published
- 1992
28. Boson–fermion and baryon mapping of multiquark states
- Author
-
Jutta Meyer
- Subjects
Condensed Matter::Quantum Gases ,Quark ,Physics ,Particle physics ,High Energy Physics::Lattice ,Statistical and Nonlinear Physics ,Fermion ,Nuclear matter ,Quantum number ,Three-body problem ,Baryon ,symbols.namesake ,Pauli exclusion principle ,symbols ,Mathematical Physics ,Boson - Abstract
The generalized Dyson boson mapping is extended to multifermion systems containing three‐particle substructures as occurring in nuclear matter. Two different approaches are described. The first one leads to a mapping involving equal numbers of bosons and fermions, where each boson, as usual, represents a fermion pair. The second possibility consists of the introduction of new kinds of fermions carrying the quantum numbers of the original three‐fermion subsystems. Both transformations are nonunitary.
- Published
- 1991
29. Cardiospecific overexpression of the prostaglandin EP3 receptor attenuates ischemia-induced myocardial injury
- Author
-
Thomas Hohlfeld, Jürgen Schrader, Christoph Jacoby, Gernot Kaber, Melanie Martin, Jutta Meyer-Kirchrath, Karsten Schrör, Ulrich Rüther, and Ulrich Flögel
- Subjects
medicine.medical_specialty ,Sodium-Hydrogen Exchangers ,G protein ,medicine.medical_treatment ,Adrenergic beta-Antagonists ,Myocardial Ischemia ,Prostaglandin ,Myocardial Reperfusion Injury ,GTP-Binding Protein alpha Subunits, Gi-Go ,Ventricular Function, Left ,Protein kinase C signaling ,chemistry.chemical_compound ,Mice ,Physiology (medical) ,Internal medicine ,Coronary Circulation ,medicine ,Animals ,Receptors, Prostaglandin E ,Transgenes ,Prostaglandin E2 ,Receptor ,Protein Kinase C ,Cardioprotection ,Mice, Inbred C3H ,business.industry ,Magnetic Resonance Imaging ,Mice, Inbred C57BL ,Endocrinology ,chemistry ,Receptors, Prostaglandin E, EP3 Subtype ,Signal transduction ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug ,Prostaglandin E ,Signal Transduction - Abstract
Background— The generation of prostaglandin E 2 (PGE 2 ) is significantly increased in acute myocardial ischemia and reperfusion. PGE 2 , in addition to other prostaglandins, protects the reperfused ischemic myocardium. It has been hypothesized that this cardioprotection is mediated by E-type prostaglandin receptors of the G i -coupled EP 3 subtype. Methods and Results— We tested this hypothesis by generating transgenic (tg) mice with cardiospecific overexpression of the EP 3 receptor. According to ligand binding, a 40-fold overexpression of the EP 3 receptor was achieved in membranes prepared from tg hearts compared with wild-type (wt) littermates. In isolated cardiomyocytes from tg mice, the forskolin-induced rise in cAMP was markedly attenuated, indicating coupling of the overexpressed EP 3 receptor to inhibitory G proteins (G i ) with constitutive receptor activity. There was no evidence for EP 3 receptor coupling to G q -mediated protein kinase C signaling. Isolated hearts from tg and wt mice were subjected to 60 minutes of no-flow ischemia and 45 minutes of reperfusion. In tg hearts, ischemic contracture was markedly delayed compared with wt hearts, and the ischemia-induced increase in left ventricular end-diastolic pressure was reduced by 55%. Creatine kinase and lactate dehydrogenase release was significantly decreased by 85% and 73%, respectively, compared with wt hearts. Conclusions— Constitutive prostaglandin EP 3 receptor signaling exerts a protective effect on cardiomyocytes, which is probably G i mediated and results in a remarkable attenuation of myocardial injury during ischemia and reperfusion. Cardioprotective actions of E-type prostaglandins may be mediated by this receptor subtype.
- Published
- 2005
30. Regulation of Thrombomodulin Expression in Human Vascular Smooth Muscle Cells by COX-2–Derived Prostaglandins
- Author
-
Jutta Meyer-Kirchrath, Artur-Aron Weber, Robert Pape, Ellen Bretschneider, Mario Sarbia, Kerstin Rabausch, Karsten Schrör, Petra Censarek, and Jens W. Fischer
- Subjects
Carotid Artery Diseases ,Vascular smooth muscle ,Pyridines ,Physiology ,Thrombomodulin ,Vasodilator Agents ,Receptors, Prostaglandin ,Prostacyclin ,Stimulation ,Second Messenger Systems ,Culture Media, Serum-Free ,Etoricoxib ,Thrombophilia ,Sulfones ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis ,Sulfonamides ,biology ,Coronary Vessels ,medicine.anatomical_structure ,Receptors, Prostaglandin E, EP3 Subtype ,Tetradecanoylphorbol Acetate ,lipids (amino acids, peptides, and proteins) ,Cardiology and Cardiovascular Medicine ,Carotid Artery, Internal ,medicine.drug ,Artery ,medicine.medical_specialty ,Diclofenac ,Myocytes, Smooth Muscle ,Models, Biological ,Dinoprostone ,Downregulation and upregulation ,medicine ,Humans ,Receptors, Prostaglandin E ,Cyclooxygenase Inhibitors ,Saphenous Vein ,Iloprost ,RNA, Messenger ,Alprostadil ,Mammary Arteries ,Blood Coagulation ,Cyclooxygenase 2 Inhibitors ,business.industry ,Gene Expression Profiling ,Colforsin ,Membrane Proteins ,Isoquinolines ,Epoprostenol ,Surgery ,Bucladesine ,Gene Expression Regulation ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Prostaglandins ,biology.protein ,Cancer research ,Cyclooxygenase ,business - Abstract
There is concern that cyclooxygenase (COX)-2 inhibitors may promote atherothrombosis by inhibiting vascular formation of prostacyclin (PGI 2 ) and an increased thrombotic risk of COX-2 inhibitors has been reported. It is widely accepted that the prothrombotic effects of COX-2 inhibitors can be explained by the removal of platelet-inhibitory PGI 2 . Using microarray chip technology, we have previously demonstrated that thrombomodulin (TM) mRNA is upregulated in cultured human coronary artery smooth muscle cells by the stable prostacyclin mimetic iloprost. This study is the first to demonstrate a stimulation of the expression of functionally active thrombomodulin in human smooth muscle cells by prostaglandins, endogenously formed via the COX-2 pathway. Because TM is an important inhibitor of blood coagulation, these findings provide a novel platelet-independent mechanism to explain the prothrombotic effects of COX-2 inhibitors. The full text of this article is available online at http://circres.ahajournals.org.
- Published
- 2005
31. Cyclooxygenase COX-2a, a novel COX-2 mRNA variant, in platelets from patients after coronary artery bypass grafting
- Author
-
Artur-Aron Weber, Thomas Hohlfeld, Jutta Meyer-Kirchrath, Michael Udelhoven, Sun-Jung Ku, Kerstin Freidel, Karsten Schrör, and Petra Censarek
- Subjects
Gene isoform ,Blood Platelets ,Pathology ,medicine.medical_specialty ,Molecular Sequence Data ,law.invention ,Frameshift mutation ,law ,medicine ,Humans ,Protein Isoforms ,Platelet ,RNA, Messenger ,Cloning, Molecular ,Coronary Artery Bypass ,Frameshift Mutation ,Sequence Deletion ,Messenger RNA ,biology ,Base Sequence ,business.industry ,Alternative splicing ,Membrane Proteins ,Hematology ,Molecular biology ,Stop codon ,Up-Regulation ,Alternative Splicing ,Codon, Nonsense ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,biology.protein ,Recombinant DNA ,Cyclooxygenase ,business - Abstract
SummaryThere are two principal cyclooxygenase isoforms referred to as COX-1 and COX-2. Recently, COX-3 has been identified. We have demonstrated the expression of COX-2 in platelets from patients after coronary artery bypass grafting (CABG). Careful biochemical analysis revealed that, when compared to recombinant COX-2, platelet COX-2 had a slightly higher electrophoretic mobility. Two COX-2 sequences (∼1.8 kb, ∼1.7 kb) were cloned from platelet mRNA. The ∼1.7 kb sequence, designated COX-2a, differed from the human COX-2 sequence only in a deletion from position +458 to +567. Similar to the human COX-3, there is a frame shift in the COX-2a sequence resulting in a TAA stop codon at position +490. Thus, the expression of a COX-2a protein corresponding to the 67 kDa COX-2 protein is not clear. However, the marked shifting from COX-2 to COX-2a in platelets from some patients after CABG is a striking finding.
- Published
- 2004
32. Analysis of mammalian gene function using small interfering RNAs
- Author
-
Henning Urlaub, Klaus Weber, Reinhard Luehrmann, Markus Hossbach, Sayda Elbashir, Javier Martinez, Thomas Tuschl, Jens Harborth, Heiko Manninga, Stephen A. Scaringe, Agnieszka Patkaniowska, Jutta Meyer, and Kim Vandenburgh
- Subjects
Gene Expression Profiling ,Animals ,General Medicine ,Small nucleolar RNA ,Biology ,RNA, Small Interfering ,Mammalian gene ,Gene ,Function (biology) ,Long non-coding RNA ,Cell biology - Published
- 2003
33. Regulation of cyclooxygenase-2 expression by iloprost in human vascular smooth muscle cells. Role of transcription factors CREB and ICER
- Author
-
Svenja, Debey, Jutta, Meyer-Kirchrath, and Karsten, Schrör
- Subjects
Time Factors ,Vasodilator Agents ,Gene Expression ,Membrane Proteins ,Epoprostenol ,Muscle, Smooth, Vascular ,Cyclic AMP Response Element Modulator ,DNA-Binding Proteins ,Isoenzymes ,Repressor Proteins ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Cyclic AMP ,Humans ,Tetradecanoylphorbol Acetate ,Iloprost ,RNA, Messenger ,Cyclic AMP Response Element-Binding Protein - Abstract
Prostaglandin-endoperoxide synthase-2 (PGH-synthase) or cyclooxygenase-2 (COX-2) is inducible by a variety of stimuli, e.g. inflammatory mediators, growth factors and hormones and is believed to be responsible for the majority of inflammatory prostanoid production. Moreover, it has been demonstrated that COX-2 contributes substantially to prostacyclin-synthesis in patients with atherosclerosis. In this study, we demonstrate an up-regulation of COX-2 mRNA, protein and product formation by the prostacyclin-mimetic iloprost in human vascular smooth muscle cells (hSMC). COX-2 mRNA expression was induced transiently between 1 and 6 hr and returned to basal levels after 16 hr of iloprost stimulation. COX-2 protein was induced concomitantly between 3 and 6 hr of iloprost stimulation. This was accompanied by an increase in PGI(2) formation. Forskolin, a direct activator of adenylyl cyclase, and dibutyryl cAMP, a cell-permeable cAMP analogue-induced COX-2 mRNA, suggesting a cAMP-dependent COX-2 expression in hSMC. Iloprost-induced COX-2 protein expression and PGI(2) formation was synergistically elevated by co-stimulation with the phorbolester PMA (phorbol-12-myristate-13-acetate). It is concluded, that the observed up-regulation of COX-2 with subsequent release of newly synthesized PGI(2) and the synergistic effect of iloprost and phorbolester on PGI(2) formation provide a positive feedback of prostaglandins on their own synthesizing enzyme. This might be important for control of hSMC proliferation, migration and differentiation as well as inhibition of platelet aggregation.
- Published
- 2003
34. A new world of tiny RNAs - siRNAs and miRNAs
- Author
-
Thomas Tuschl, Mariana Lagos-Quintana, Kim Bechert, Javier Martinez, Jens Harborth, Jutta Meyer, Klaus Weber, Sayda Elbashir, Agnieszka Patkaniowska, and Abdullah Yalcin
- Subjects
microRNA ,Computational biology ,Biology - Published
- 2002
35. Activation of IP and EP(3) receptors alters cAMP-dependent cell migration
- Author
-
Rüdiger Blindt, Peter Hanrath, Thomas Hohlfeld, Anja-K. Bosserhoff, Jürgen vom Dahl, Jutta Meyer-Kirchrath, and Karsten Schrör
- Subjects
Agonist ,Neointima ,medicine.medical_specialty ,Smooth muscle cell migration ,medicine.drug_class ,Receptors, Prostaglandin ,Prostacyclin ,CHO Cells ,Biology ,Receptors, Epoprostenol ,Muscle, Smooth, Vascular ,Cell Movement ,Internal medicine ,Cricetinae ,medicine ,Cyclic AMP ,Animals ,Humans ,Receptors, Prostaglandin E ,Iloprost ,Receptor ,Cells, Cultured ,Pharmacology ,Chemotaxis ,Cell migration ,Cell biology ,Endocrinology ,Receptors, Prostaglandin E, EP3 Subtype ,cardiovascular system ,medicine.drug - Abstract
Migration of vascular smooth cells from the media to the intima essentially contributes to neointima formation after percutaneous transluminal angioplasty and stent implantation. The stable prostacyclin mimetic iloprost has been shown to inhibit neointima formation in experimental restenosis, but it is currently unknown whether this may be caused by an antimigratory effect. Hence, the present study analyses (i) the influence of G(s)-coupled prostacyclin (IP) receptors on cell migration and (ii) verifies whether EP(3) receptors with opposite (i.e., G(i)) coupling may conversely stimulate cell migration. In a modified Boyden chamber model, it was shown that iloprost dose-dependently inhibits the migration of primary human arterial smooth muscle cells, which constitutively express the IP receptor. On the other hand, human arterial smooth muscle cell migration was stimulated by the EP(3) receptor agonist M&B 28.767. To independently study the effects of these receptors, IP or EP(3) receptors were stably overexpressed in chinese hamster ovary cells (CHO-IP and CHO-EP(3)). Chemotaxis of CHO cells transfected with G(s)-coupled IP receptors was concentration-dependently inhibited by iloprost (2-100 nM), while there was no effect of iloprost on mock-transfected CHO. By contrast, CHO-cells that overexpressed EP(3) receptors showed a significant, concentration dependent (1-100 nM) increase of cell migration in presence of the selective EP(3) agonist M&B 28.767. It is concluded that the prostacyclin mimetic iloprost inhibits vascular cell migration, which probably depends on a G(s)-mediated increase of intracellular cAMP. EP(3) receptors conversely stimulate CHO migration.
- Published
- 2002
36. Prostacyclin enhances the expression of LPS/INF-gamma-induced nitric oxide synthase in human monocytes
- Author
-
Bernd Grabensee, Chunmei Huang, Karsten Schrör, Jörg Plum, and Jutta Meyer-Kirchrath
- Subjects
Lipopolysaccharides ,medicine.medical_specialty ,Lipopolysaccharide ,medicine.medical_treatment ,Receptors, Prostaglandin ,Nitric Oxide Synthase Type II ,Prostacyclin ,Biology ,Peritonitis ,Nitric Oxide ,Receptors, Epoprostenol ,Monocytes ,Nitric oxide ,chemistry.chemical_compound ,Interferon-gamma ,Mediator ,Internal medicine ,medicine ,Cyclic AMP ,Macrophage ,Humans ,RNA, Messenger ,Cells, Cultured ,Monocyte ,Molecular biology ,Epoprostenol ,Nitric oxide synthase ,medicine.anatomical_structure ,Endocrinology ,Cytokine ,chemistry ,biology.protein ,Nitric Oxide Synthase ,medicine.drug - Abstract
Background: Nitric oxide (NO) is an important mediator of inflammatory processes, including macrophage-mediated cellular host defense, and is found to be increased in peritonitis. The ability of human mononuclear cells to contribute to the NO production by expression of active inducible NO synthase (iNOS) is still discussed controversely. Aims: This study was designed to investigate the influence of prostacyclin receptor (IP receptor) activation on iNOS expression and NO formation in human peripheral blood monocytes. Method and Results: Using reverse transcriptase-polymerase chain reaction, we demonstrated that human monocytes express high levels of IP receptor mRNA. Stimulation of monocytes with the IP receptor selective agonist cicaprost (100 nM) significantly induced cellular cyclic adenosine monophosphate formation, indicating functional coupling of the receptor to Gs. Treatment of cells with lipopolysaccharide (LPS)/interferon gamma (IFN-γ) further enhanced the IP receptor mRNA expression 2.7 ± 0.1-fold above basal levels (n = 6). Analysis of iNOS expression revealed barely detectable mRNA levels in unstimulated monocytes which were increased 3.75 ± 0.3-fold (n = 5) after costimulation with 1 µg/ml LPS and 250 U/ml INF-γ for 16 h. Further increases of iNOS mRNA expression (9.4 ± 0.9-fold above basal, n = 5) were obtained, if the monocytes were costimulated with 1 µg/ml LPS, 250 U/ml INF-γ, and 100 nM cicaprost for 16 h. Measurement of the NO generation correlated with the polymerase chain reaction data: treatment of cells with 1 µg/ml LPS plus 250 U/ml INF-γ increased the NO2 production to 2.6 µM, being above the basal level of 2.0 µM, as determined in the cell culture medium. Additional treatment with 100 nM cicaprost further significantly increased the NO2 production to 3.43 µM. Conclusions: An IP receptor mediated increase in cyclic adenosine monophosphate formation plays an important role in enhancing LPS/IFN-γ-induced iNOS expression in human monocytes/macrophages and may, therefore, contribute to the increased production of NO during peritonitis.
- Published
- 2002
37. Identification of tissue-specific microRNAs from mouse
- Author
-
Winfried Lendeckel, Abdullah Yalcin, Thomas Tuschl, Jutta Meyer, Mariana Lagos-Quintana, and Reinhard Rauhut
- Subjects
Genetics ,education.field_of_study ,Lin-4 microRNA precursor ,Agricultural and Biological Sciences(all) ,Base Sequence ,Biochemistry, Genetics and Molecular Biology(all) ,Population ,Molecular Sequence Data ,Sequence Analysis, DNA ,Biology ,Genome ,General Biochemistry, Genetics and Molecular Biology ,Mice ,MicroRNAs ,Mirtron ,Organ Specificity ,microRNA ,MiR-122 ,Gene silencing ,Animals ,Human genome ,Tissue Distribution ,Cloning, Molecular ,General Agricultural and Biological Sciences ,education - Abstract
MicroRNAs (miRNAs) are a new class of noncoding RNAs, which are encoded as short inverted repeats in the genomes of invertebrates and vertebrates [1, 2]. It is believed that miRNAs are modulators of target mRNA translation and stability, although most target mRNAs remain to be identified. Here we describe the identification of 34 novel miRNAs by tissue-specific cloning of approximately 21-nucleotide RNAs from mouse. Almost all identified miRNAs are conserved in the human genome and are also frequently found in nonmammalian vertebrate genomes, such as pufferfish. In heart, liver, or brain, it is found that a single, tissue-specifically expressed miRNA dominates the population of expressed miRNAs and suggests a role for these miRNAs in tissue specification or cell lineage decisions. Finally, a miRNA was identified that appears to be the fruitfly and mammalian ortholog of C. elegans lin-4 stRNA.
- Published
- 2002
38. Selective cyclooxygenase-2 inhibition upregulates renal cortical alpha V integrin expression
- Author
-
Christoph, Waldner, Gunhild, Heise, Jutta, Meyer-Kirchrath, Karsten, Schrör, Bernd, Grabensee, and Peter, Heering
- Subjects
Sulfonamides ,Kidney Cortex ,Cyclooxygenase 2 Inhibitors ,Kidney Glomerulus ,Integrin alphaV ,Gene Expression Regulation, Enzymologic ,Rats ,Up-Regulation ,Isoenzymes ,Glomerulonephritis ,Gene Expression Regulation ,Celecoxib ,Cyclooxygenase 2 ,Prostaglandin-Endoperoxide Synthases ,Prostaglandins ,Animals ,Pyrazoles ,Cyclooxygenase Inhibitors ,Female ,Prospective Studies ,RNA, Messenger ,Rats, Wistar - Abstract
Cyclooxygenase-2 (COX-2), the inducible isoform of the cyclooxygenases, is upregulated in various inflammatory renal diseases and responsible for prostaglandin formation. As prostaglandins are known to influence cell adhesion processes, we investigated the effect of COX-2 inhibition on the expression of alpha(v) integrins, which are also enhanced in renal diseases and control the adherence between the endothelium and the extracellular matrix (ECM) in the glomerulus.Healthy female Wistar rats and animals with previously induced passive Heymann nephritis (PHN) received either 5 mg/kg body weight/day celecoxib or a placebo. After 28 days, renal cortical mRNA expression of COX-2 and alpha(v) integrin subunits was determined.Rats with PHN showed a significant 1.7-fold increase in renal cortical mRNA expression of alpha(v) integrin subunits. Treatment with celecoxib increased cortical alpha(v) integrin mRNA expression 2.2-fold (p0.05) in healthy animals and 4.0-fold (p0.05) in rats with PHN, but lowered COX-2 mRNA expression in rats with PHN to 0.8-fold (p0.05). An inverse correlation between the expression of COX-2 and alpha(v) integrins in rats with PHN was demonstrated.It is suggested that COX-2-derived prostaglandins suppress the expression of alpha(v) integrins. This implies a previously unknown role for COX-2 in chronic inflammation in the kidney.
- Published
- 2002
39. Characterization of the Prostaglandin EP3-Receptor from Porcine Heart
- Author
-
Karsten Schrör, Thomas Hohlfeld, and Jutta Meyer
- Subjects
Gene isoform ,genomic DNA ,Transmembrane domain ,cDNA library ,Complementary DNA ,Intron ,lipids (amino acids, peptides, and proteins) ,Genomic library ,Biology ,Receptor ,Molecular biology - Abstract
Protection of the myocardium from ischemic injury by prostacyclins and PGE1 has been repeatedly reported. Part of the antiischemic effects may be mediated by cardiac sarcolemmal EP3-receptors which have been characterized earlier in this laboratory by ligand binding studies. Of particular notice is the presence of multiple EP3 isoforms, e. g. in mouse, cattle and man which are generated by differential splicing. Here we describe the cloning and subtype characterization of the porcine EP3-receptor. We obtained two different isoforms of the receptor by screening a porcine heart cDNA library. The predicted receptor proteins consisted of 395 and 387 amino acids, respectively, with differences only in the C-terminal part of the protein. Several overlapping genomic clones were obtained from a porcine genomic library. Sequence comparison of the cDNA with the genomic DNA indicated that an intron was located in the region corresponding to the sixth transmembrane domain of the receptor protein. This position exactly matches the corresponding intron in the human TXA2-, the human PGD2- and the mouse PGE-receptor (EP1-subtype). In further experiments, we expressed the porcine EP3-receptor in COS-7 cells and performed ligand-binding-studies. In addition the expression of the porcine EP3-receptor mRNA in different tissues was demonstrated by RT-PCR.
- Published
- 1997
40. Cyclooxygenase-2 in human platelets as a possible factor in aspirin resistance
- Author
-
Jutta Meyer-Kirchrath, Artur-Aron Weber, Katja C. Zimmermann, and Karsten Schrör
- Subjects
medicine.medical_specialty ,biology ,Vascular disease ,business.industry ,General Medicine ,Pharmacology ,medicine.disease ,Thrombosis ,Negative therapeutic reaction ,Endocrinology ,Internal medicine ,Chemoprophylaxis ,medicine ,biology.protein ,Platelet ,Cyclooxygenase ,business ,ASPIRIN RESISTANCE - Published
- 1999
41. H. Reichenbach and O. B. Weeks (Editors), The Flavobacterium-Cytophaga Group (Proceedings of the International Symposium on Yellow-Pigmented Gram-Negative Bacteria of the Flavobacterium-Cytophaga Group, to 11 July 1980, Braunschweig-Stöckheim). 217 S., 7
- Author
-
Jutta Meyer
- Subjects
Gram-negative bacteria ,Cytophaga ,biology ,Group (periodic table) ,Chemistry ,Genetics ,Physiology ,General Medicine ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Flavobacterium ,Microbiology - Published
- 2007
42. Expression of calcification-relevant factors is reduced by prostacyclin in human vascular smooth muscle cells
- Author
-
Jutta Meyer-Kirchrath, Jens W. Fischer, Christian Glandorff, and Karsten Schrör
- Subjects
Pharmacology ,medicine.medical_specialty ,Endocrinology ,Vascular smooth muscle ,Physiology ,Chemistry ,Internal medicine ,medicine ,Molecular Medicine ,Prostacyclin ,medicine.disease ,Calcification ,medicine.drug - Published
- 2006
43. High rate of somatic point mutation in vitro in and near the variable-region segment of an immunoglobulin heavy chain gene
- Author
-
Hans-Martin Jäck, N Ellis, Jutta Meyer, and Matthias Wabl
- Subjects
Genetics ,Base Composition ,Multidisciplinary ,Base Sequence ,Point mutation ,Immunoglobulin Variable Region ,Somatic hypermutation ,Locus (genetics) ,DNA ,Biology ,Molecular biology ,Stop codon ,DNA sequencing ,Cell Line ,Mutation ,Immunoglobulin heavy chain ,Cloning, Molecular ,Allele ,Codon ,Immunoglobulin Heavy Chains ,Gene ,Research Article - Abstract
The "silent" allele at the immunoglobulin heavy-chain locus in the pre-B-lymphocyte line 18-81 contains a correctly assembled gene. However, an amber termination codon within the variable-region gene segment prematurely terminates translation into complete heavy chain. Revertants that do produce heavy chain are generated at a high rate, which is termed hypermutation. By DNA sequencing of subclones, we have confirmed that whenever mu chain is produced by the usually silent allele, a true reversion is found in the DNA. Mutations are not confined to the position of the amber termination codon but are also found at other sites in and near the variable-region gene segment.
- Published
- 1986
44. New species of the genus Actinomadura
- Author
-
Jutta Meyer
- Subjects
Type (biology) ,Taxon ,Botany ,Genetics ,Bacterial taxonomy ,Morphology (biology) ,Biology ,Applied Microbiology and Biotechnology ,Soil microbiology ,Genus Actinomadura ,Spore - Abstract
Several strains, which according to their cell wall type and morphology belong to the genus Actinomadura, differ markedly from already recognized species. They are considered to be new taxa: A. libanotica, A. ferruginea, and A. spiralis. Their descriptions and illustrations are presented.
- Published
- 1979
45. Contribution to the taxonomy of methanotrophic bacteria: Correlation between membrane type and GC-value
- Author
-
W. Böckel, J. Heyer, R. Haubold, and Jutta Meyer
- Subjects
food.ingredient ,Classification scheme ,General Medicine ,Biology ,biology.organism_classification ,Applied Microbiology and Biotechnology ,Microbiology ,Archaeobacteria ,chemistry.chemical_compound ,Membrane ,food ,Biochemistry ,chemistry ,Methylocystis ,Taxonomy (biology) ,Bacteria ,Cytosine ,DNA - Abstract
Thirty-nine isolates and additional reference strains of methanotrophic bacteria were studied with respect to mol % G + C of their DNA and the type of intracytoplasmatic membranes. The results on the whole confirm the former classification scheme of Whittenbury et al. (1970). However, problematic groups such as “Methylocystis” and “Methylobacter” are in need of additional taxonomic studies.
- Published
- 1986
46. Vλ2 rearranges with all functional Jλ segments in the mouse
- Author
-
Siegfried Weiss, M. R. Wabl, and Jutta Meyer
- Subjects
Immunology ,Immunology and Allergy ,Gene rearrangement ,Biology ,Lambda ,Molecular biology ,Recombination ,Southern blot - Abstract
We have analyzed 210 lambda-producing hybridomas derived from lipopolysaccharide-stimulated spleen cells from a single kappa-suppressed mouse. All were classified as lambda 1, lambda 2 or lambda 3 with the exception of four unusual lines. Two of these were due to V lambda 2 J lambda 1 and the other two to V lambda 2 J lambda 3 rearrangements. The lines were clonally independent since the point of VJ recombination in each one was different. Southern blot analysis of the V lambda 2 C lambda 1-producing lines showed no evidence for an inversion. Under the assumption of a simple deletion model of rearrangement these findings place the V lambda 2 cluster upstream of the V lambda 1 cluster oriented in the same direction.
- Published
- 1985
47. New species of the genusActinomadura
- Author
-
Jutta Meyer
- Subjects
Spores, Bacterial ,Actinomycetales ,Genetics ,General Medicine ,Biology ,Applied Microbiology and Biotechnology ,Soil Microbiology ,Culture Media - Published
- 1979
48. Eignung von Esterase-Mustern als taxonomisches Kriterium bei Actinomyceten
- Author
-
Jutta Meyer
- Subjects
Chemistry ,Genetics ,Applied Microbiology and Biotechnology - Published
- 1969
49. Critical test of a sister chromatid exchange model for the immunoglobulin heavy-chain class switch
- Author
-
Jutta Meyer, Matthias Wabl, Maria Tenkhoff, Peter D. Burrows, and Gabriele B. Beck-Engeser
- Subjects
Recombination, Genetic ,Genetics ,Multidisciplinary ,Immunoglobulin mu-Chains ,Immunoglobulin gamma-Chains ,Sister chromatid exchange ,Gene rearrangement ,Biology ,Models, Biological ,Isotype ,Mice ,chemistry.chemical_compound ,Restriction map ,Genes ,chemistry ,Animals ,Immunoglobulin heavy chain ,Chromatid ,Chromosome Deletion ,Immunoglobulin Heavy Chains ,Sister Chromatid Exchange ,Gene ,DNA - Abstract
B lymphocytes may switch from producing an immunoglobulin heavy chain of the mu class to that of the gamma, epsilon or alpha class. To maintain the specificity, the new heavy chain must keep the original variable (V) region; this is achieved by deleting DNA sequences so that the V (consisting of joined VH, diversity (DH) and joining (JH) gene segments) and C (constant) gene segments coding for the new heavy chain are brought into close proximity (reviewed in ref. 5; we do not consider here the mu-delta situation). There are, in principle, three types of chromosomal rearrangements that yield a deletion: rearrangement within a chromatid; unequal sister chromatid exchange (as suggested by Obata et al.); and unequal recombination between chromosomal homologues. We have analysed the arrangement of C mu DNA in clones of the pre-B-cell line 18-81 that switches in vitro from mu to gamma 2b. The clones examined produce either mu, gamma 2b or no immunoglobulin chain. We report here that all the gamma 2b clones had lost at least one copy of C mu and no clones contained three copies of C mu. These findings formally exclude both unequal sister chromatid exchange and recombination between homologues as mechanisms for creating a gene encoding the gamma 2b chain.
- Published
- 1985
50. Seminal prostaglandins in men with subnormal sperm motility and therapeutic treatment
- Author
-
Jutta Meyer and Werner Schlegel
- Subjects
Infertility ,Male ,medicine.medical_specialty ,Varicocele ,Motility ,Alpha (ethology) ,Prostaglandin ,Fructose ,Biology ,Dinoprost ,Biochemistry ,Dinoprostone ,chemistry.chemical_compound ,Endocrinology ,Semen ,Internal medicine ,medicine ,Humans ,Testosterone ,Sperm motility ,Infertility, Male ,Sperm Count ,Prostaglandins E ,Prostaglandins F ,Radioimmunoassay ,Kallikrein ,medicine.disease ,Epoprostenol ,Prolactin ,chemistry ,Prostaglandins ,Sperm Motility ,lipids (amino acids, peptides, and proteins) ,Kallikreins ,circulatory and respiratory physiology - Abstract
The contents of prostaglandins in seminal plasma from a total of 73 men were evaluated. The subjects were grouped as follows: normospermic men, patients with impaired motility, patients with small untreated varicocele and patients with impaired motility and Kallikrein therapy. Sperm density, morphology and motility were examined. High performance reversed phase liquid chromatography (HPLC) in combination with specific radioimmunoassays were used for the determination of PGE2, PGI2 and PGF2 alpha. There was a significant difference (p less than 0.025; F-test) between the PGI2 concentrations in patients with impaired motility (5.6 +/- 1.4 pg/mg protein) and normal men (8.8 +/- 3.7 pg/mg protein). PGE2 and PGF2 alpha were significantly different in patients with varicocele (p less than 0.025, F-test). Wide ranges of prostaglandins occurred in the Kallikrein-group with no significant differences. We conclude that: a) PGI2 is an additional prostaglandin compound in seminal plasma, b) its measurement may not be useful as diagnostic parameter in subfertile men and c) Kallikrein has no influence on the prostaglandin content in seminal plasma and other seminal parameters as motility, motility index and sperm counts.
- Published
- 1986
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