A5032990574- Cancer, Hypoxia, and Metabolism
- Acute Kidney Injury Research
- High Altitude and Hypoxia
- Dialysis and Renal Disease Management
- Eicosanoids and Hypertension Pharmacology
- Chronic Kidney Disease and Diabetes
- Renal function and acid-base balance
- Trauma, Hemostasis, Coagulopathy, Resuscitation
- Renal and related cancers
- Sepsis Diagnosis and Treatment
- Metabolism, Diabetes, and Cancer
- Electrolyte and hormonal disorders
- MRI in cancer diagnosis
- Mitochondrial Function and Pathology
- Genetic and Kidney Cyst Diseases
- Erythropoietin and Anemia Treatment
- Respiratory Support and Mechanisms
- Fibroblast Growth Factor Research
- Adipose Tissue and Metabolism
- Cardiac Arrest and Resuscitation
- Angiogenesis and VEGF in Cancer
- Head and Neck Cancer Studies
- COVID-19 Clinical Research Studies
- Renal cell carcinoma treatment
- Poisoning and overdose treatments
Universitätsklinikum Erlangen
2015-2025
Friedrich-Alexander-Universität Erlangen-Nürnberg
2015-2025
Friedrich Schiller University Jena
2024
Jena University Hospital
2024
Essen University Hospital
2022
University Hospital Ulm
2016
University Hospital and Clinics
2012-2015
University Medical Center
2012-2015
Hypertension Institute
2006-2013
Charité - Universitätsmedizin Berlin
1998-2005
Dendritic cells (DC) play a key role in linking innate and adaptive immunity. In inflamed tissues, where DC become activated, oxygen tensions are usually low. Although hypoxia is increasingly recognized as an important determinant of cellular functions, the consequences one players hypoxic gene regulation, transcription factor inducible 1alpha (HIF-1alpha), largely unknown. Thus, we investigated effects HIF-1alpha on murine activation function presence or absence exogenous inflammatory...
Activation of hypoxia-inducible transcription factor (HIF) has been identified as an important mechanism cellular adaptation to low oxygen. Normoxic degradation HIF is mediated by oxygen-dependent hydroxylation specific prolyl residues the regulative alpha-subunits hydroxylases (PHD). It was hypothesized that inhibition either hypoxia or pharmacologic PHD would confer protection against subsequent ischemic injury. For testing this hypothesis acute renal failure induced in rats 40 min...
Hypoxia-inducible transcription factors (HIF) mediate complex adaptations to reduced oxygen supply, including neoangiogenesis. Regulation of HIF occurs mainly through oxygen-dependent destruction its alpha subunit. In the presence oxygen, two HIFalpha prolyl residues undergo enzymatic hydroxylation, which is required for proteasomal degradation. We therefore tested whether pharmacological activation by hydroxylase inhibitors may provide a novel therapeutic strategy treatment ischemic...
The contribution of hypoxia to cisplatin-induced renal tubular injury is controversial. Because the hypoxia-inducible factor (HIF) pathway a master regulator adaptation hypoxia, we measured effects cisplatin on HIF accumulation in vitro and vivo, tested whether hypoxic preconditioning protective against injury. We found that did not stabilize HIF-1alpha protein or vivo under normoxic conditions. However, cisplatin-treated proximal cells culture reduced apoptosis an HIF-1alpha-dependent...
Hypoxia inducible factor (HIF) is regulated by dual pathways involving oxygen-dependent prolyl and asparaginyl hydroxylation of its α-subunits. Prolyl at two sites within a central degradation domain promotes association HIF-α with the von Hippel-Lindau ubiquitin E3 ligase destruction ubiquitin-proteasome pathways. Asparaginyl blocks recruitment p300/CBP co-activators to C-terminal activation in HIF-α. These hydroxylations are catalyzed members Fe(II) 2-oxoglutarate (2-OG) oxygenase family....
Long-term survival of renal allografts depends on the chronic immune response and is probably influenced by initial injury caused ischemia reperfusion. Hypoxia-inducible transcription factors (HIFs) are essential for adaptation to low oxygen. Normoxic inactivation HIFs regulated oxygen-dependent hydroxylation specific prolyl-residues prolyl-hydroxylases (PHDs). Pharmacological inhibition PHDs results in HIF accumulation with subsequent activation tissue-protective genes. We examined effect...
Both hypoxic and inflammatory conditions activate transcription factors such as hypoxia-inducible factor (HIF)-1α nuclear (NF)-κB, which play a crucial role in adaptive responses to these challenges. In dendritic cells (DC), lipopolysaccharide (LPS)-induced HIF1α accumulation requires NF-κB signaling promotes DC function. The mechanisms that drive LPS-induced under normoxia are unclear. Here, we demonstrate LPS inhibits prolyl hydroxylase domain enzyme (PHD) activity thereby blocks...
New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by concentration effects chronic insufficiency. This study therefore directly compared the performance AKI plasma.This single-center, prospective cohort included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 2010. Plasma and/or concentrations creatinine, cystatin C,...
BNP (brain-type natriuretic peptide) is a cardiac hormone with systemic haemodynamic effects as well local cytoprotective and antiproliferative properties. It induced under variety of pathophysiological conditions, including decompensated heart failure myocardial infarction. Since regional hypoxia potential common denominator increased wall stretch hypoperfusion, we investigated the direct on expression, role HIF (hypoxia-inducible transcription factor) in regulation. Using an RNase...
ABSTRACT HIF1A is a transcription factor that plays central role for the adaptation to tissue hypoxia and inflammatory response of myeloid cells, including DCs. stabilized by but also TLR ligands under normoxic conditions. The underlying signaling events leading accumulation in presence oxygen are still poorly understood. Here, we show contrast hypoxic stabilization HIF1A, normoxic, TLR-mediated DCs follows different pathway predominantly requires MYD88-dependent NF-κB activity. TLR-induced...
Hypoxia-inducible transcription factors (HIF) protect cells against oxygen deprivation, and HIF stabilization before ischemia mitigates tissue injury. Because ischemic acute kidney injury (AKI) often involves the thick ascending limb (TAL), modulation of in this segment may be protective. Here, we generated mice with targeted TAL deletion von Hippel-Lindau protein (Vhl), which mediates degradation under normoxia, using Tamm-Horsfall (Thp)-driven Cre expression. These showed strong expression...
The Hypoxia-inducible transcription Factor (HIF) represents an important adaptive mechanism under hypoxia, whereas sustained activation may also have deleterious effects. HIF activity is determined by the oxygen regulated α-subunits HIF-1α or HIF-2α. Both are dependent degradation, which controlled tumor suppressor "von Hippel-Lindau" (VHL), gatekeeper of renal tubular growth control. appears to play a particular role for kidney, where EPO production, organ preservation from...
Background.Inhibition of the HIF regulating prolyl hydroxylation domain (PHDs) proteins prior to renal injury (preconditioning) has been shown protect kidney via activation hypoxia-inducible transcription factors (HIF). Application erythropoietin (EPO), one target genes, also be nephroprotective, and it remains unclear what extent effect induction is mediated by EPO. It unknown whether after onset ischaemia (postconditioning) still able kidney.
Abstract Introduction Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal is often paralleled a combined respiratory metabolic acidosis. We assessed the effectiveness of hollow-fiber gas exchanger integrated into conventional renal-replacement circuit on CO 2 removal, acidosis, hemodynamics. Methods In ten ventilated critically ill AKI undergoing renal- respiratory-replacement therapy, effects low-flow removal acidosis compensation were tested by using...
Abstract —The tyrosine kinase receptor Tie2 (also known as Tek) plays an important role in the development of embryonic vasculature and persists adult endothelial cells (ECs). was shown to be upregulated tumors skin wounds, its ligands angiopoietin-1 -2, although they are not directly mitogenic, modulate neovascularization. To gain further insight into regulation Tie2, we have studied effect hypoxia inflammatory cytokines, two conditions frequently associated with neoangiogenic processes, on...
Hypoxia-inducible factor-1 (HIF) is a transcription factor central to oxygen homeostasis. It regulated via its α isoforms. In normoxia they are ubiquitinated by the von Hippel-Lindau E3 ligase complex and destroyed proteasome, thereby preventing formation of an active transcriptional complex. Oxygen-dependent enzymatic hydroxylation either two critical prolyl residues in each HIFα chain has recently been identified as modification necessary for targeting Here we demonstrate that polypeptides...