CD95 Ligand (Fas-L/APO-1L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Mediate Ischemia-Induced Apoptosis in Neurons

Ana Martin-Villalba; Ingrid Herr; Irmela Jeremias; Michael Hahne; Roland Brandt; Johannes Vogel; Johannes Schenkel; Thomas Herdegen; Klaus-Michael Debatin

doi:10.1523/JNEUROSCI.19-10-03809.1999

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CD95 Ligand (Fas-L/APO-1L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Mediate Ischemia-Induced Apoptosis in Neurons

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CD95 Ligand (Fas-L/APO-1L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Mediate Ischemia-Induced Apoptosis in Neurons

Ana Martin-Villalba, Ingrid Herr, Irmela Jeremias, Michael Hahne, Roland Brandt, Johannes Vogel, Johannes Schenkel, Thomas Herdegen et Klaus-Michael Debatin

The Journal of neuroscience, Vol.19(10), pp.3809-3817

15/05/1999

DOI: https://doi.org/10.1523/JNEUROSCI.19-10-03809.1999

PMID: 10234013

Résumé

Programmed cell death plays an important role in the neuronal degeneration after cerebral ischemia, but the underlying mechanisms are not fully understood. Here we examined, in vivo andin vitro, whether ischemia-induced neuronal death involves death-inducing ligand/receptor systems such as CD95 and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). After reversible middle cerebral artery occlusion in adult rats, both CD95 ligand and TRAIL were expressed in the apoptotic areas of the postischemic brain. Further recombinant CD95 ligand and TRAIL proteins induced apoptosis in primary neurons and neuron-like cells in vitro. The immunosuppressant FK506, which most effectively protects against ischemic neurodegeneration, prevented postischemic expression of these death-inducing ligands both in vivo and in vitro. FK506 also abolished phosphorylation, but not expression, of the c-Jun transcription factor involved in the transcriptional control of CD95 ligand. Most importantly, in lpr mice expressing dysfunctional CD95, reversible middle cerebral artery occlusion resulted in infarct volumes significantly smaller than those found in wild-type animals. These results suggest an involvement of CD95 ligand and TRAIL in the pathophysiology of postischemic neurodegeneration and offer alternative strategies for the treatment of cardiovascular brain disease.

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Titre: CD95 Ligand (Fas-L/APO-1L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Mediate Ischemia-Induced Apoptosis in Neurons
Créateurs - sans rôle: Ana Martin-Villalba - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Ingrid Herr - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Irmela Jeremias - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Michael Hahne - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Roland Brandt - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Johannes Vogel - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Johannes Schenkel - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Thomas Herdegen - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Klaus-Michael Debatin - Departments of Physiology and Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany, Division of Molecular Oncology, Deutsches Krebsforschungszentrum, D-69120 Heidelberg, Germany, Department of Pharmacology, University of Kiel, D-24118 Kiel, Germany, and Department of Biochemistry, University of Lausanne, CH-1000 Lausanne, Switzerland
Détails de publication: The Journal of neuroscience, Vol.19(10), pp.3809-3817
Éditeur: Society for Neuroscience
Nombre de pages: 9
Identifiants: 99153924809311
Unité académique: Institut de Génétique Moléculaire de Montpellier - IGMM
Langue: English
Type de ressource: Journal article