Marcel Leist

Measurement of cellular beta-site of APP cleaving enzyme 1 activity and its modulation in neuronal assay systems (2009)

Volbracht, Christiane, Penzkofer, Stephan, Mansson, David, Vielsted Christensen, Kenneth, Fog, Karina, Schildknecht, Stefan, ...

Amyloid-β peptide (Aβ), a putatively causative agent of Alzheimer’s disease (AD), is proteolytically derived from β-amyloid precursor protein (APP). Here we describe cellular assays...

High-dose erythropoietin alters platelet reactivity and bleeding time in rodents in contrast to the neuroprotective variant carbamyl-erythropoietin (CEPO) (2008)

Kirkeby, Agnete, Torup, Lars, Bochsen, Louise, Kjalke, Marianne, Abel, Kristin, Theilgaard-Monch, Kim, ...

The haematopoietic hormone erythropoietin (EPO) has neuroprotective properties and is currently being explored for treatment of stroke and other neurological disorders. Short-term, high-dose...

The dawning of a new age of toxicology (2008)

Leist, Marcel, Hartung, Thomas, Nicotera, Pierluigi

Toxicology faces enormous challenges in a world in which we are exposed to thousands of chemicals and millions of mixtures thereof. Radically new approaches to this problem need to be developed. A...

Vor- und Nachdenkliches ... zum wahren Erfolg des 3R-Prinzips (2008)

Leist, Marcel, Kadereit, Suzanne, Schildknecht, Stefan

Ist es möglich, den "Wert" einer wissenschaftlichen Disziplin zu bemessen? Wie kann diese Disziplin dann in einem Gesamtrahmen eingeordnet werden, und nicht zuletzt, ist eine solche Überlegung...

The biological and ethical basis of the use of human embryonic stem cells for in vitro test systems or cell therapy (2008)

Leist, Marcel, Bremer, Susanne, Brundin, Patrik, Hescheler, Jürgen, Kirkeby, Agnete, Krause, Karl-Heinz, ...

Human embryonic stem cells (hESC) are now routinely cultured in many laboratories, and differentiation protocols are available to generate a large variety of cell types. In an ongoing ethical debate...

Food for Thought ... on the Real Success of 3R Approches (2008)

Leist, Marcel, Kadereit, Suzanne, Schildknecht, Stefan

Can the value of a scientific discipline be gauged? Where does the discipline stand? Is such a consideration important at all? Some may have doubts about the usefulness of asking such questions. Some...

Vor- und Nachdenkliches ... zur Evolution der Toxikologie und dem Ausstieg aus Tierversuchen (2008)

Hartung, Thomas, Leist, Marcel

Auf dem Gebiet der Toxikologie tut sich etwas: Die Vision und Strategie der US National Academy of Sciences (NRC, 2007) aus dem letzten Jahr hat viele Toxikologen auf beiden Seiten des Atlantiks...

Food for thought … on the evolution of toxicology and the phasing out of animal testing (2008)

Hartung, Thomas, Leist, Marcel

There is something brewing in the field of toxicology: Last year's vision and strategy document published by the US National Academy of Sciences (NRC, 2007) has excited many toxicologists on both...

Vesicular monoamine transporter 2 regulates the sensitivity of rat dopaminergic neurons to disturbed cytosolic dopamine levels (2007)

Vergo, Sandra, Johansen, Jens Leander, Leist, Marcel, Lotharius, Julie

An abnormal accumulation of cytosolic dopamine resulting in reactive oxygen species and dopamine–quinone productsmay play an important role in the rather selective degeneration of substantia nigra...

Functional and immunochemical characterisation of different antibodies against the erythropoietin receptor (2007)

Kirkeby, Agnete, Beek, Johan Van, Nielsen, Jacob, Leist, Marcel, Helboe, Lone

Since it was discovered that the hematopoietic hormone erythropoetin (EPO) exerts neuroprotective effects in the CNS, many studies on the EPO receptor (EPOR) function and localisation in the CNS have...

Reduced functional deficits, neuroinflammation, and secondary tissue damage after treatment of stroke by nonerythropoietic erythropoietin derivatives (2007)

Villa, Pia, Beek, Johan Van, Larsen, Anna Kirstine, Gerwien, Jens, Christensen, Søren, Cerami, Anthony, ...

Carbamylerythropoietin (CEPO) does not bind to the classical erythropoietin (EPO) receptor. Nevertheless, similarly to EPO, CEPO promotes neuroprotection on the histologic level in short-term stroke...

Pathological apoptosis in the developing brain (2007)

Blomgren, Klas, Leist, Marcel, Groc, Laurent

More than half of the initially-formed neurons are deleted in certain brain regions during normal development. This process, whereby cells are discretely removed without interfering with the further...

Neuroprotective properties of memantine in different in vitro and in vivo models of excitotoxicity (2006)

Volbracht, Christiane, Beek, Johan Van, Zhu, Changlian, Blomgren, Klas, Leist, Marcel

The pathogenesis of stroke, trauma and chronic degenerative diseases, such as Alzheimer’s disease (AD), has been linked to excitotoxic processes due to inappropriate stimulation of the...

Increased erythropoietin production after myocardial infarction in mice (2006)

Mengozzi, M., Latini, Renato, Salio, M., Sfacteria, Alessandra, Piedimonte, G., Gammeltoft Gerwien, Jens, ...

In addition to its role as the main regulator of erythropoiesis, erythropoietin has a wide range of protective, antiapoptotic activities in vitro and in vivo, particularly in the brain and, as more...

Nonhematopoietic Erythropoietin Derivatives Prevent Motoneuron Degeneration In Vitro and In Vivo (2006)

Mennini, Tiziana, Paola, Massimiliano De, Bigini, Paolo, Mastrotto, Cristina, Fumagalli, Elena, Barbera, Sara, ...

Chronic treatment with asialo erythropoietin (ASIALO-EPO) or carbamylated erythropoietin (CEPO) improved motor behavior and reduced motoneuron loss and astrocyte and microglia activation in the...

Comparison of neuroprotective effects of erythropoietin (EPO) and carbamylerythropoietin (CEPO) against ischemia-like oxygen–glucose deprivation (OGD) and NMDA excitotoxicity in mouse hippocampal slice cultures (2006)

Montero, Maria, Rom Poulsen, Frantz, Noraberg, Jens, Kirkeby, Agnete, Beek, Johan Van, Leist, Marcel, ...

In addition to its well-known hematopoietic effects, erythropoietin (EPO) also has neuroprotective properties. However, hematopoietic side effects are unwanted for neuroprotection, underlining the...

A role for mixed lineage kinases in granule cell apoptosis induced by cytoskeletal disruption (2006)

Müller, Georg Johannes, Geist, Marie Aavang, Veng, Lone Merete, Willesen, Mette Georgi, Johansen, Flemming Fryd, Leist, Marcel, ...

Microtubule disruption by colchicine induces apoptosis in selected neuronal populations. However, little is known about the upstream death signalling events mediating the neurotoxicity. We...

The dynamics of the LPS triggered inflammatory response of murine microglia under different culture and in vivo conditions (2006)

Lund, Søren, Vielsted Christensen, Kenneth, Hedtjärn, Maj, Mortensen, Anne-Louise, Hagberg, Henrik, Falsig, Jeppe, ...

Overall, the inflammatory potential of lipopolysaccharide (LPS) in vitro and in vivo was investigated using different omics technologies. We investigated the hippocampal response to...

The inflammatory transcriptome of reactive murine astrocytes and implications for their innate immune function (2006)

Falsig, Jeppe, Pörzgen, Peter, Lund, Søren, Schrattenholz, André, Leist, Marcel

Upon injury, astrocytes assume an activated state associated with the release of inflammatory mediators. To model this, we stimulated murine primary astrocytes with a complete inflammatory cytokine...

Development of Non-Erythropoietic Erythropoietin Variants for Neuroprotection (2006)

Torup, Lars, Leist, Marcel

Erythropoietin is well known to possess erythropoietic activity, but also tissue protection. Here, we present examples on how to separate these two activities. One possibility is to generate a...

Progressive Degeneration of Human Mesencephalic Neuron Derived Cells Triggered by Dopamine-Dependent Oxidative Stress Is Dependent on the Mixed-Lineage Kinase Pathway (2005)

Lotharius, Julie, Falsig, Jeppe, Beek, Johan Van, Payne, Sarah, Dringen, Ralf, Brundin, Patrik, ...

Models of Parkinson's disease (PD) based on selective neuronal death have been used to study pathogenic mechanisms underlying nigral cell death and in some instances to develop symptomatic therapies....

Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis (2005)

Berliocchi, Laura, Fava, Eugenio, Leist, Marcel, Horvat, Volker, Dinsdale, David, Read, David, ...

Clostridial neurotoxins are bacterial endopeptidases that cleave the major SNARE proteins in peripheral motorneurons. Here, we show that disruption of synaptic architecture by botulinum neurotoxin C1...

Inhibition of microglial inflammation by the MLK inhibitor CEP-1347 (2005)

Lund, Søren, Porzgen, Peter, Mortensen, Anna-Louise, Hasseldam, Henrik, Bozyczko-Coyne, Donna, Morath, Siegfried, ...

CEP-1347 is a potent inhibitor of the mixed lineage kinases (MLKs), a distinct family of mitogen-activated protein kinase kinase kinases (MAPKKK). It blocks the activation of the c-Jun/JNK apoptotic...

Asialoerythropoetin is not effective in the R6/2 line of Huntington's disease mice (2004)

Gil, Joana MAC, Leist, Marcel, Popovic, Natalija, Brundin, Patrik, Petersén, Åsa

Abstract Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. Both excitotoxicity and oxidative stress have been proposed...

The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin (2004)

Wang, Xiaoyang, Zhu, Changlian, Wang, Xinhua, Gerwien, Jens Gammeltoft, Schrattenholz, Andre, Sandberg, Mats, ...

Recently, erythropoietin (EPO) and the nonerythropoietic derivative asialoEPO have been linked to tissue protection in the nervous system. In this study, we tested their effects in a model of...

Asialoerythropoetin is not effective in the R6/2 line of Huntington's disease mice (2004)

Gil, Joana MAC, Leist, Marcel, Popovic, Natalija, Brundin, Patrik, Petersén, Åsa

Background: Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an expanded CAG repeat in the HD gene. Both excitotoxicity and oxidative stress have been proposed to play...

Poly(ADP-ribose) glycohydrolase as a target for neuroprotective intervention : assessment of currently available pharmacological tools (2004)

Falsig, Jeppe, Hofman Christiansen, Søren, Feuerhahn, Sascha, Bürkle, Alexander, Li Oei, Shiao, Keil, Claudia, ...

Poly(ADP-ribose) glycohydrolase (PARG) is being considered as a therapeutic target for the prevention of neurodegeneration. Here, we assessed the pharmacological tools available for target...

Lysosomes in cell death (2004)

Guicciardi, Maria Eugenia, Leist, Marcel, Gores, Gregory J.

For many years apoptosis research has focused on caspases and their putative role as sole executioners of programmed cell death. Accumulating information now suggests that lysosomal cathepsins are...

Modification of apoptosis-related genes and CD95 signaling in cytokine-treated astrocytes (2004)

Falsig, Jeppe, Pörzgen, Peter, Leist, Marcel

Inflammatory activation of astrocytes with a complete cytokine mix consisting of tumor necrosis factor, interleukin-1 and interferon-gamma renders these otherwise resistant cells highly susceptible...

Defined inflammatory states in astrocyte cultures: correlation with susceptibility towards CD95-driven apoptosis (2004)

Falsig, Jeppe, Latta, Markus, Leist, Marcel

A complete cytokine mix (CCM) or its individual components tumour necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interferon-gamma (IFN-γ) were used to switch resting...

Specific Modulation of Astrocyte Inflammation by Inhibition of Mixed Lineage Kinases with CEP-1347 (2004)

Falsig, Jeppe, Pörzgen, Peter, Lotharius, Julie, Leist, Marcel

Inflammatory conversion of murine astrocytes correlates with the activation of various MAPK, and inhibition of terminal MAPKs like JNK or p38 dampens the inflammatory reaction. Mixed lineage kinases...

Sensitization to the Lysosomal Cell Death Pathway upon Immortalization and Transformation (2004)

Fehrenbacher, Nicole, Gyrd-Hansen, Mads, Poulsen, Birgit, Felbor, Ute, Kallunki, Tuula, Boes, Marianne, ...

Tumorigenesis is associated with several changes that alter the cellular susceptibility to programmed cell death. Here, we show that immortalization and transformation sensitize cells in particular...

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo (2003)

Erbayraktar, Serhat, Grasso, Giovanni, Sfacteria, Alessandra, Xie, Qiao-Wen, Coleman, Thomas, Kreilgaard, Mads, ...

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects...

Overexpression of heat shock protein 70 in R6 / 2 Huntington’s disease mice has only modest effects on disease progression (2003)

Hansson, Oskar, Nylandsted, Jesper, Castilho, Roger F., Leist, Marcel, Jäätela, Marja, Brundin, Patrik

Huntington’s disease (HD) is a neurodegenerative disorder caused by expansion of a polyglutamine tract in a protein called huntingtin. The inducible form of heat shock protein 70 (Hsp70) has been...

Rapid, noninflammatory and PS-dependent phagocytic clearance of necrotic cells (2003)

Hirt, U. A., Leist, Marcel

In pathological situations, different modes of cell death are observed, and information on the role and uptake of nonapoptotic corpses is scarce. Here, we modeled two distinct forms of death in human...

Caspase-independent cell death (2002)

Leist, Marcel, Jäättelä, Marja

Caspase-mediated apoptosis is the death program of choice in many developmental and physiologic settings. It would, however, be very dangerous for the organism to depend on a single protease family...

Mitogen-Activated Protein Kinase-Activated Protein Kinase 2-Deficient Mice Show Increased Susceptibility to Listeria monocytogenes Infection (2002)

Lehner, Martin D., Schwoebel, Frank, Kotlyarov, Alexey, Leist, Marcel, Gaestel, Matthias, Hartung, Thomas

Mitogen-activated protein kinase-activated protein kinase 2 (MK2) is one of several kinases activated through direct phosphorylation by p38 mitogen-activated protein kinase. MK2 regulates LPS-induced...

Burning up TNF toxicity for cancer therapy (2002)

Leist, Marcel, Jäättelä, Marja

The tumor-killing capacity and the systemic toxicity of the cytokine tumor necrosis factor (TNF) have appeared inseparable. Now a study shows that TNF loses its toxicity but still kills tumors in...

Eradication of Glioblastoma, and Breast and Colon Carcinoma Xenografts by Hsp70 Depletion (2002)

Nylandsted, Jesper, Wick, Wolfgang, Hirt, Ulrich A., Brand, Karsten, Rohde, Mikkel, Leist, Marcel, ...

Heat shock protein 70 (Hsp70) is an antiapoptotic chaperone protein highly expressed in human tumors. Here we demonstrate that locoregional application of adenovirus expressing antisense Hsp70 cDNA...

Calpain inhibitors prevent nitric oxidetriggered excitotoxic apoptosis (2001)

Volbracht, Christiane, Fava, Eugenio, Leist, Marcel, Nicotera, Pierluigi

The pathogenesis of some neurodegenerative disorders has been linked to excitotoxicity, excess generation of nitric oxide (NO) and apoptosis. Here, we used a model of NO-triggered neuronal apoptosis...

Apoptosis in Caspase-inhibited Neurons (2001)

Volbracht, Christiane, Leist, Marcel, Kolb, Stefan A., Nicotera, Pierluigi

Background: There is growing evidence of apoptosis in neurodegenerative disease. However, it is still unclear whether the pathological manifestations observed in slow neurodegenerative diseases are...

Cathepsin B Acts as a Dominant Execution Protease in Tumor Cell Apoptosis Induced by Tumor Necrosis Factor (2001)

Foghsgaard, Lasse, Wissing, Dorte, Mauch, Daniel, Boes, Marianne, Elling, Folmer, Leist, Marcel, ...

Death receptors can trigger cell demise dependent or independent of caspases. In WEHI-S fibrosarcoma cells, tumor necrosis factor (TNF) induced an increase in cytosolic cathepsin B activity followed...

Synthesis of Ganglioside GD3 and its Comparison with Bovine GD3 with Regard to Oligodendrocyte Apoptosis Mitochondrial Damage (2001)

Castro-Palomino, Julio C., Simon, Bernadett, Speer, Oliver, Leist, Marcel, Schmidt, Richard R.

2,3-Dehydroneuraminic acid derivative 5 was transformed in five efficient steps into sialyl donor 2, which has a phenylthio group on the b-side of the 3-position for anchimeric assistance and a...

Caspase-3 activity is present in cerebrospinal fluid from patients with traumatic brain injury (2001)

Härter, Luc, Keel, Marius, Hentze, Hannes, Leist, Marcel, Ertel, Wolfgang

Loss of neurons after traumatic brain injury (TBI) might involve dysregulated apoptosis. Activation of caspase-3 is one hallmark of apoptosis. Therefore, caspase-3 activity (cleavage of DEVD-afc) was...

Metabolic Depletion of ATP by Fructose Inversely Controls CD95- and Tumor Necrosis Factor Receptor 1–mediated Hepatic Apoptosis (2000)

Latta, Markus, Künstle, Gerald, Leist, Marcel, Wendel, Albrecht

Hepatocyte apoptosis is crucial in several forms of liver disease. Here, we examined in different models of murine liver injury whether and how metabolically induced alterations of hepatocyte ATP...

Age-related Macular Degeneration : the Lipofuscin Component N-Retinyl-N-Retinylidene Ethanolamine Detaches Proapoptotic Proteins from Mitochondria and Induces Apoptosis in Mammalian Retinal Pigment Epithelial Cells (2000)

Suter, Marianne, Remé, Charlotte, Grimm, Christian, Wenzel, Andreas, Jäättela, Marja, Esser, Peter, ...

10–20% of individuals over the age of 65 suffer from agerelated macular degeneration (AMD), the leading cause of severe visual impairment in humans living in developed countries. The pathogenesis of...

Energy Requirement for Caspase Activation and Neuronal Cell Death (2000)

Nicotera, Pierluigi, Leist, Marcel, Fava, Eugenio, Berliocchi, Laura, Volbracht, Christiane

Recent work has shown that execution of the apoptotic program involves a relatively limited number of pathways. According to a general view, these would converge to activate the caspase family of...

Phagocytosis of Nonapoptotic Cells Dying by Caspase-Independent Mechanisms (2000)

Hirt, Ulrich, Gantner, Florian, Leist, Marcel

Caspase activation, exposure of phosphatidylserine (PS) on the outer surface of the plasma membrane, and rapid phagocytic removal of dying cells are key features of apoptosis. Nonapoptotic/necrotic...

ATP Controls Neuronal Apoptosis Triggered by Microtubule Breakdown or Potassium (1999)

Volbracht, Christiane, Leist, Marcel, Nicotera, Pierluigi

Background: Early loss of neurites followed by delayed damage of neuronal somata is a feature of several neurodegenerative diseases. Death by apoptosis would ensure the rapid removal of injured...

Selective Nitration of Prostacyclin Synthase and Defective Vasorelaxation in Atherosclerotic Bovine Coronary Arteries (1999)

Leist, Marcel, Ullrich, Volker, Zou, Ming-Hui

Prostacyclin synthase (PCS) is an enzyme with antithrombotic, antiproliferative, and dilatory functions in the normal vasculature, and inactivation of PCS by tyrosine nitration may favor...

The Expression of Plasma Membrane Ca2+ Pump Isoforms in Cerebellar Granule Neurons Is Modulated by Ca²+ (1999)

Guerini, Danilo, García-Martin, Elena, Gerber, Andreas, Volbracht, Christiane, Leist, Marcel, Gutiérrez Merino, Carlos, ...

Plasma membrane Ca²+ ATPase (PMCA) pump isoforms 2, 3, and 1CII are expressed in large amounts in the cerebellum of adult rats but only minimally in neonatal cerebellum. These isoforms were almost...

Nitric Oxide Inhibits Execution of Apoptosis at Two Distinct ATP-Dependent Steps Upstream and Downstream of Mitochondrial Cytochrome c Release (1999)

Leist, Marcel, Single, Barbara, Naumann, Heike, Fava, Eugenio, Simon, Bernadett, Kühnle, Simone

The endogenous mediator nitric oxide (NO) blocked apoptosis of Jurkat cells elicited by staurosporine, anti-CD95 or chemotherapeutics, and switched death to necrosis. The switch in the mode of cell...

Transgenic mice expressing a Huntington’s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity (1999)

Hansson, Oskar, Petersén, Åsa, Leist, Marcel, Nicotera, Pierluigi, Castilho, Roger F., Brundin, Patrik

Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant...

Tributyltin-Induced Apoptosis Requires Glycolytic Adenosine Trisphosphate Production (1999)

Stridh, Hélène, Fava, Eugenio, Single, Barbara, Nicotera, Pierluigi, Orrenius, Sten, Leist, Marcel

The toxicity of tributyltin chloride (TBT) involves Ca2+ overload, cytoskeletal damage, and mitochondrial failure leading to cell death by apoptosis or necrosis. Here, we examined whether the...

1-Methyl-4-Phenylpyridinium Induces Autocrine Excitotoxicity, Protease Activation, and Neuronal Apoptosis (1998)

Leist, Marcel, Volbracht, Christiane, Fava, Eugenio, Nicotera, Pierluigi

The pathogenesis of several neurodegenerative diseases may involve indirect excitotoxic mechanisms, where glutamate receptor overstimulation is a secondary consequence of initial functional defects...

Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice (1998)

Steinbach, Joachim P., Müller, Ulrike, Leist, Marcel, Li, Zhi-Wei, Nicotera, Pierluigi, Aguzzi, Adriano

Secreted forms of the β-amyloid precursor protein (β-APP) have neuroprotective properties in vitro and may be involved in the containment of neuronal excitation. To test whether loss of...

Simultaneous release of adenylate kinase and cytochrome c in cell death (1998)

Single, Barbara, Leist, Marcel, Nicotera, Pierluigi

Cytochrome c (Cyt c) is located within the mitochondrial intermembrane space, and it is an essential constituent of the respiratory chain. The translocation of Cyt c from mitochondria to the cytosol...

Differentiation Between Apoptotic and Necrotic Cell Death by Means of the BM Cell Death Detection ELISA or Annexin V Staining (1998)

Leist, Marcel, Kühnle, Simone, Single, Barbara, Nicotera, Pierluigi

Apoptosis and necrosis are two forms of cell death that have been defined on the basis of distinguishable morphological criteria. However, these different types of cell death may involve several...

Cytokine-Mediated Hepatic Apoptosis (1998)

Leist, Marcel, Gantner, Florian, Künstle, Gerald, Wendel, Albrecht

Thirty years ago liver pathology defined apoptosis as a novel mode of cell death. Recently, experimental models of liver injury have been made available for examining the signaling molecules and...

Intracellular Adenosine Triphosphate (ATP) Concentration : A Switch in the Decision Between Apoptosis and Necrosis (1997)

Leist, Marcel, Single, Barbara, Castoldi, Anna F., Kühnle, Simone, Nicotera, Pierluigi

Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers...

Caspase-Mediated Apoptosis in Neuronal Excitotoxicity Triggered by Nitric Oxide (1997)

Leist, Marcel, Volbracht, Christiane, Kühnle, Simone, Fava, Eugenio, Ferrando-May, Elisa, Nicotera, Pierluigi

BACKGROUND: Excitotoxicity and excess generation of nitric oxide (NO) are believed to be fundamental mechanisms in many acute and chronic neurodegenerative disorders. Disturbance of Ca2+ homeostasis...

Peroxynitrite and Nitric Oxide Donors Induce Neuronal Apoptosis by Eliciting Autocrine Excitotoxicity (1997)

Leist, Marcel, Fava, Eugenio, Montecucco, Cesare, Nicotera, Pierluigi

Endogenous generation of nitric oxide and its congeners, including peroxynitrite (ONOO-), has been implicated in the mechanism of neuron loss in neurodegenerative diseases. Accordingly, nitric oxide...

The novel SAR-binding domain of scaffold attachment factor A (SAF-A) is a target in apoptotic nuclear breakdown (1997)

Göhring, Frank, Schwab, Birgit L., Nicotera, Pierluigi, Leist, Marcel, Fackelmayer, Frank O.

The scaffold attachment factor A (SAF-A) is an abundant component of the nuclear scaffold and of chromatin, and also occurs in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes. Evidence from...

Detectable concentrations of Fas ligand in cerebrospinal fluid after severe head injury (1997)

Ertel, Wolfgang, Keel, Marius, Stocker, Reto, Imhof, Hans-Georg, Leist, Marcel, Steckholzer, Ursula, ...

When the cell surface molecule Fas is triggered by its agonist Fas ligand the result is apoptosis of these cells and tissue destruction. To elucidate the pathophysiological relevance of Fas ligand in...

Tumor necrosis factor-induced apoptosis during the poisoning of mice with hepatotoxins (1997)

Leist, Marcel, Gantner, Florian, Naumann, Heike, Bluethmann, Horst, Vogt, Kathrin, Brigelius-Flohe, Regina, ...

BACKGROUND & AIMS: Treatment with tumor necrosis factor (TNF) induces murine hepatocyte apoptosis in vitro and in vivo when sensitizing concentrations of toxins are present. The aim of this study was...

Energy supply and the shape of death in neurons and lymphoid cells (1997)

Nicotera, Pierluigi, Leist, Marcel

Apoptosis and necrosis are considered as conceptually distinct forms of cell death. Nevertheless, there is increasing evidence that classical apoptosis and necrosis represent only the extreme ends of...

The Shape of Cell Death (1997)

Leist, Marcel, Nicotera, Pierluigi

Cell death, a scheduled event during development and tissue turnover, or the ultimate consequence of toxic or pathologic insults seems to involve a relatively limited number of execution pathways....

ICE-protease inhibitors block murine liver injury and apoptosis caused by CD95 or by TNF-alpha (1997)

Künstle, Gerald, Leist, Marcel, Uhlig, Stefan, Revesz, Laszlo, Feifel, Roland, MacKenzie, Andrew, ...

The two apoptosis receptors of mammalian cells, i.e. the 55 kDa TNF receptor (TNF-R1) and CD95 (Fas/APO1) are activated independently of each other, however, their signaling involves a variety of...

Cytoskeletal Breakdown and Apoptosis Elicited by NO Donors in Cerebellar Granule Cells Require NMDA Receptor Activation (1996)

Bonfoco, Emanuela, Leist, Marcel, Zhivotovsky, Boris, Orrenius, Sten, Lipton, Stuart A., Nicotera, Pieriuigi

We have recently demonstrated that nitric oxide (NO) donors can trigger either apoptosis or necrosis of neurons as a function of the intensity of the exposure. Here, we show that the apoptosis...

A novel mechanism of murine hepatocyte death inducible by Concanavalin A (1996)

Leist, Marcel, Wendel, Albrecht

Background: Concanavalin A (Con A) is a plant lectin that polyclonally activates T-cells. When given intravenously to mice it induces a selective liver failure. Hepatotoxicity following Con A...

Tumor necrosis factor production in the perfused mouse liver and its pharmacological modulation by methylxanthines (1996)

Leist, Marcel, Auer-Barth, Sigrid, Wendel, Albrecht

The liver contains the largest pool of cytokine-producing macrophages in the body and may therefore play an important role in the development and outcome of systemic inflammatory response syndromes....

DNA Fragmentation In Mouse Organs during Endotoxic Shock (1996)

Bohlinger, Ines, Leist, Marcel, Gantner, Florian, Angermüller, Sabine, Tiegs, Gisa, Wendel, Albrecht

The systemic inflammatory response syndrome has still an unpredictable outcome, and patients often die of multiple organ failure despite circulatory stabilization therapy. The still incompletely...

T Cell Stimulus-Induced Crosstalk between Lymphocytes and Liver Macrophages Results in Augmented Cytokine Release (1996)

Gantner, Florian, Leist, Marcel, Küsters, Sabine, Vogt, Katrin, Volk, Hans-Dieter, Tiegs, Gisa

Polyclonal T cell stimulation in humans leads to a cytokine burst syndrome that may result in organ failure or lethality. Mechanisms of such cytokine-dependent morbidity can be studied in mice...

Enhanced Release of Interleukin-10 and Soluble Tumor Necrosis Factor Receptors as Novel Principles of Methylxanthine Action in Murine Models of Endotoxic Shock (1996)

Jilg, Sabine, Barsig, Johannes, Leist, Marcel, Küsters, Sabine, Volk, Hans-Dieter, Wendel, Albrecht

The immunomodulating capacity of the methylxanthine A802715 (5-hydroxy- 5-methyl)hexyl-3-methyl-7-propylxanthin) was investigated in various murine models of endotoxemia and compared with that of the...

Concanavalin A - induced T-cell - mediated hepatic injury in mice : The role of tumor necrosis factor (1995)

Gantner, Florian, Leist, Marcel, Lohse, Ansgar Wilhelm, Germann, Paul Georg, Tiegs, Gisa

Concanavalin A activates T lymphocytes in vitro and causes T-cell-dependent hepatic injury in mice. T lymphocytes were previously identified as effector cells of concanavalin A-induced liver injury....

Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models (1995)

Leist, Marcel, Gantner, Florian, Bohlinger, Ines, Tiegs, Gisa, Germann, Paul Georg, Wendel, Albrecht

We investigated the role of hepatocyte apoptosis in four different murine models of acute inflammatory liver failure. Liver damage induced in D-galactosamine-sensitized mice by endotoxin infection...

Tunicamycin potently inhibits tumor necrosis factor-induced hepatocyte apoptosis (1995)

Leist, Marcel, Wendel, Albrecht

The protein glycosylation inhibitor tunicamycin protected male BALB/c mice from tumor necrosis factor α-induced liver failure. Tunicamycin also inhibited tumor necrosis factor-induced cell death...

Tolerance against tumor necrosis factor alpha (TNF)-induced hepatotoxicity in mice : the role of nitric oxide (1995)

Bohlinger, Ines, Leist, Marcel, Barsig, Johannes, Uhlig, Stefan, Tiegs, Gisa, Wendel, Albrecht

D-Galactosamine-sensitized mice challenged with tumor necrosis factor α (TNF) developed severe apoptotic and secondary necrotic liver injury as assessed by histology, measurement of cytosolic...

Interleukin-1 and nitric oxide protect against tumor necrosis factor alpha induced liver injury through distinct pathways (1995)

Bohlinger, Ines, Leist, Marcel, Barsig, Johannes, Uhlig, Stefan, Tiegs, Gisa, Wendel, Albrecht

Mice sensitized with D-galactosamine (GalN) and challenged with recombinant murine tumor necrosis factor α (TNFα) developed severe apoptotic and secondary necrotic liver injury as assessed...

Isolation and characterization of rat primary lung cells (1995)

Bundschuh, Daniela S., Uhlig, Stefan, Leist, Marcel, Sauer, Achim, Wendel, Albrecht

Lung cell culture may be useful as anin vitro alternative to study the susceptibility of the lung to various toxic agents. Lungs from female Wistar rats were enzymatically digested by recirculating...

Activation of the 55 kDa TNF receptor is necessary and sufficient for TNF-induced liver failure, hepatocyte apoptosis, and nitrite release (1995)

Leist, Marcel, Gantner, Florian, Jilg, Sabine, Wendel, Albrecht

The systemic inflammatory response is characterized by release of circulating TNF which may cause multiorgan failure including septic liver failure. We studied TNF signaling in an appropriate in...

Murine hepatocyte apoptosis induced in vitro and in vivo by TNF-alpha requires transcriptional arrest (1994)

Leist, Marcel, Gantner, Florian, Bohlinger, Ines, Germann, Paul G., Tiegs, Gisa, Wendel, Albrecht

Freshly isolated mouse hepatocytes were essentially insensitive to TNF- alpha cytotoxicity. However, TNF-alpha induced a concentration- dependent cell death in hepatocytes that had been pretreated...

Transgenic mice expressing a Huntington’s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

Hansson, Oskar, Petersén, Åsa, Leist, Marcel, Nicotera, Pierluigi, Castilho, Roger F., Brundin, Patrik

Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant...

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

Erbayraktar, Serhat, Grasso, Giovanni, Sfacteria, Alessandra, Xie, Qiao-wen, Coleman, Thomas, Kreilgaard, Mads, ...

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects...

Nonhematopoietic Erythropoietin Derivatives Prevent Motoneuron Degeneration In Vitro and In Vivo

Mennini, Tiziana, De Paola, Massimiliano, Bigini, Paolo, Mastrotto, Cristina, Fumagalli, Elena, Barbera, Sara, ...

Chronic treatment with asialo erythropoietin (ASIALO-EPO) or carbamylated erythropoietin (CEPO) improved motor behavior and reduced motoneuron loss and astrocyte and microglia activation in the...

Transgenic mice expressing a Huntington’s disease mutation are resistant to quinolinic acid-induced striatal excitotoxicity

Hansson, Oskar, Petersén, Åsa, Leist, Marcel, Nicotera, Pierluigi, Castilho, Roger F., Brundin, Patrik

Huntington’s disease (HD) is a hereditary neurodegenerative disorder presenting with chorea, dementia, and extensive striatal neuronal death. The mechanism through which the widely expressed mutant...

Asialoerythropoietin is a nonerythropoietic cytokine with broad neuroprotective activity in vivo

Erbayraktar, Serhat, Grasso, Giovanni, Sfacteria, Alessandra, Xie, Qiao-wen, Coleman, Thomas, Kreilgaard, Mads, ...

Erythropoietin (EPO) is a tissue-protective cytokine preventing vascular spasm, apoptosis, and inflammatory responses. Although best known for its role in hematopoietic lineages, EPO also affects...

Nonhematopoietic Erythropoietin Derivatives Prevent Motoneuron Degeneration In Vitro and In Vivo

Mennini, Tiziana, De Paola, Massimiliano, Bigini, Paolo, Mastrotto, Cristina, Fumagalli, Elena, Barbera, Sara, ...

Chronic treatment with asialo erythropoietin (ASIALO-EPO) or carbamylated erythropoietin (CEPO) improved motor behavior and reduced motoneuron loss and astrocyte and microglia activation in the...

Selective Nitration of Prostacyclin Synthase and Defective Vasorelaxation in Atherosclerotic Bovine Coronary Arteries

Zou, Ming-Hui, Leist, Marcel, Ullrich, Volker

Prostacyclin synthase (PCS) is an enzyme with antithrombotic, antiproliferative, and dilatory functions in the normal vasculature, and inactivation of PCS by tyrosine nitration may favor...

Botulinum neurotoxin C initiates two different programs for neurite degeneration and neuronal apoptosis

Berliocchi, Laura, Fava, Eugenio, Leist, Marcel, Horvat, Volker, Dinsdale, David, Read, David, ...

Clostridial neurotoxins are bacterial endopeptidases that cleave the major SNARE proteins in peripheral motorneurons. Here, we show that disruption of synaptic architecture by botulinum neurotoxin C1...

Intracellular Adenosine Triphosphate (ATP) Concentration: A Switch in the Decision Between Apoptosis and Necrosis

Leist, Marcel, Single, Barbara, Castoldi, Anna F., Kühnle, Simone, Nicotera, Pierluigi

Apoptosis and necrosis are considered conceptually and morphologically distinct forms of cell death. Here, we report that demise of human T cells caused by two classic apoptotic triggers...

Metabolic Depletion of Atp by Fructose Inversely Controls Cd95- and Tumor Necrosis Factor Receptor 1–Mediated Hepatic Apoptosis

Latta, Markus, Künstle, Gerald, Leist, Marcel, Wendel, Albrecht

Hepatocyte apoptosis is crucial in several forms of liver disease. Here, we examined in different models of murine liver injury whether and how metabolically induced alterations of hepatocyte ATP...

Cathepsin B Acts as a Dominant Execution Protease in Tumor Cell Apoptosis Induced by Tumor Necrosis Factor

Foghsgaard, Lasse, Wissing, Dorte, Mauch, Daniel, Lademann, Ulrik, Bastholm, Lone, Boes, Marianne, ...

Death receptors can trigger cell demise dependent or independent of caspases. In WEHI-S fibrosarcoma cells, tumor necrosis factor (TNF) induced an increase in cytosolic cathepsin B activity followed...