A5090895071- Cell death mechanisms and regulation
- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- ATP Synthase and ATPases Research
- Autophagy in Disease and Therapy
- Cancer, Hypoxia, and Metabolism
- Pancreatic function and diabetes
- Phagocytosis and Immune Regulation
- Endoplasmic Reticulum Stress and Disease
- RNA Interference and Gene Delivery
- Cancer Immunotherapy and Biomarkers
- Metabolism, Diabetes, and Cancer
- Cancer-related Molecular Pathways
- RNA regulation and disease
- Glioma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Erythrocyte Function and Pathophysiology
- Gut microbiota and health
- Lipid Membrane Structure and Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Analytical Chemistry and Sensors
- Adipose Tissue and Metabolism
- Amyotrophic Lateral Sclerosis Research
- Cell Image Analysis Techniques
Royal College of Surgeons in Ireland
2015-2024
Czech Academy of Sciences, Institute of Physiology
2014
University of Münster
2007
University Hospital Münster
2003
Keio University
2003
Center for Clinical Research (United States)
2001-2002
Case Western Reserve University
2001
University of Bremen
2001
Activation of effector caspases is considered to be the final step in many apoptosis pathways. We transfected HeLa cells with a recombinant caspase substrate composed cyan and yellow fluorescent protein linker peptide containing cleavage sequence DEVD, we examined kinetics at single-cell level by fluorescence resonance energy transfer (FRET) analysis. Caspase activation response tumor necrosis factor-α, staurosporine, or etoposide resulted subsequent disruption FRET signal. The time varied...
High brightness, chemical and photostability, tunable characteristics, spectral surface properties are important attributes for nanoparticle probes designed live cell imaging. We describe a class of nanoparticles high-resolution imaging O2 that consists substituted conjugated polymer (polyfluorene or poly(fluorene-alt-benzothiadiazole)) acting as FRET antenna fluorescent reference with covalently bound phosphorescent metalloporphyrin (PtTFPP, PtTPTBPF). The prepared from such copolymers by...
In response to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) lumen, three ER transmembrane signaling proteins, inositol-requiring enzyme 1 (IRE1), PRKR-like kinase (PERK), and activating transcription factor 6α (ATF6α), are activated. These initiate a transcriptional network termed protein (UPR), which re-establishes cellular proteostasis. When this restoration fails, however, cells undergo apoptosis. To investigate cross-talk between these different UPR enzymes,...
We examined the temporal and causal relationship between Smac/DIABLO release, cytochrome c (cyt-c) caspase activation at single cell level during apoptosis. Cells treated with broad-spectrum inhibitor z-VAD-fmk, caspase-3 (Casp-3)–deficient MCF-7 cells, as well Bax-deficient DU-145 cells released cyt-c in response to proapoptotic agents. Real-time confocal imaging of stably expressing Smac/DIABLO-yellow fluorescent protein (YFP) revealed that average duration Smac/DIABLO-YFP release was...
A failure of mitochondrial bioenergetics has been shown to be closely associated with the onset apoptotic and necrotic neuronal injury. Here, we developed an automated computational model that interprets single-cell fluorescence for tetramethylrhodamine methyl ester (TMRM) as a consequence changes in either ΔΨ m or p , thus allowing characterization responses populations single cells subsequent statistical analysis. Necrotic injury triggered by prolonged glutamate excitation resulted rapid...
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disorder affecting motoneurons. Mutations in angiogenin , encoding a member of the pancreatic RNase A superfamily, segregate with ALS. We previously demonstrated that administration shows promise as neuroprotective therapeutic studies using transgenic ALS mice and primary motoneuron cultures. Its mechanism action target cells spinal cord, however, are largely unknown. Using mixed cultures, motoneuron-like NSC34 cells,...
Discovery of a new HDAC6 inhibitor reveals role for in the regulation glycolytic metabolism.
Little is known about the temporal relationship between mitochondrial and plasma membrane potential changes outer permeabilization during apoptosis. Confocal imaging of breast carcinoma HeLa cells stably transfected with cytochrome-C-GFP demonstrated that mitochondria rapidly depolarized after release fusion protein into cytosol. Of note, did not completely depolarize but established a new steady-state level could be further dissipated by treatment protonophore carbonyl cyanide...
Excitotoxicity resulting from excessive Ca 2+ influx through glutamate receptors contributes to neuronal injury after stroke, trauma, and seizures. Increased cytosolic levels activate a family of calcium-dependent proteases with papain-like activity, the calpains. Here we investigated role calpain activation during NMDA-induced excitotoxic in embryonic (E16–E18) murine cortical neurons that (1) underwent necrosis, characterized by immediate deregulation homeostasis, persistent depolarization...
Excitotoxicity is a condition occurring during cerebral ischemia, seizures, and chronic neurodegeneration. It characterized by overactivation of glutamate receptors, leading to excessive Ca(2+)/Na(+) influx into neurons, energetic stress, subsequent neuronal injury. We others have previously investigated populations study how bioenergetic parameters determine injury; however, such experiments are often confounded population-based heterogeneity the contribution effects non-neuronal cells....
Excessive Ca(2+) entry during glutamate receptor overactivation ("excitotoxicity") induces acute or delayed neuronal death. We report here that deficiency in bax exerted broad neuroprotection against excitotoxic injury and oxygen/glucose deprivation mouse neocortical neuron cultures reduced infarct size, necrotic injury, cerebral edema formation after middle artery occlusion mice. Neuronal mitochondrial membrane potential (Δψm) analysis revealed bax-deficient neurons showed significantly...
Exposure of rat hippocampal neurons or human D283 medulloblastoma cells to the apoptosis-inducing kinase inhibitor staurosporine induced rapid cytochrome c release from mitochondria and activation executioner caspase-3. Measurements cellular tetramethylrhodamine ethyl ester fluorescence subsequent simulation changes based on Nernst calculations in extracellular, cytoplasmic, mitochondrial compartments revealed that was preceded by hyperpolarization. Overexpression anti-apoptotic protein...
Employing fluorescence resonance energy transfer (FRET) imaging, we previously demonstrated that effector caspase activation is often an all-or-none response independent of drug choice or dose administered. We here investigated the signaling dynamics during apoptosis initiation via tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor pathway to investigate how variability in exposure can be translated into largely kinetically invariant cell death execution pathways....
Article1 March 2011Open Access Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release Heinrich J Huber Systems Biology Group, Department Physiology and Medical Physics, Royal College Surgeons in Ireland, Dublin, Ireland Search for more papers by this author Heiko Dussmann Seán M Kilbride Markus Rehm Jochen H Prehn Corresponding Author Information Huber1,‡, Dussmann1,‡, Kilbride1, Rehm1 1 1Systems ‡These authors contributed equally work...
// Federico Lucantoni 1, 2 , Heiko Düssmann Irene Llorente-Folch and Jochen H.M. Prehn 1 Department of Physiology & Medical Physics, Royal College Surgeons in Ireland, Dublin 2, Ireland Center for Systems Medicine, Correspondence to: Prehn, email: jprehn@rcsi.ie Keywords: breast cancer; BCL2 inhibitors; cell death; bioenergetics; OXPHOS Received: January 16, 2018 Accepted: April 28, Published: May 25, ABSTRACT Cancer cells display differences regarding their engagement glycolytic vs....
Breast cancer cells have different requirements on metabolic pathways in order to sustain their growth. Triple negative breast (TNBC), an aggressive subtype relies mainly glycolysis, while estrogen receptor positive (ER+) possess higher mitochondrial oxidative phosphorylation (OXPHOS) levels. However, generally employ both needs and compete with the surrounding environment. In this study, we demonstrate that fission inhibitor MDIVI-1 alters bioenergetics, at concentrations do not affect...