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Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway.
J Biol Chem. 2004 Jul 30; 279(31):32869-81.JB

Abstract

We have previously shown that two tumor necrosis factor (TNF) receptors (TNFR) exhibit antagonistic functions during neurodegenerative processes in vivo with TNFR1 aggravating and TNFR2 reducing neuronal cell loss, respectively. To elucidate the neuroprotective signaling pathways of TNFR2, we investigated glutamate-induced excitotoxicity in primary cortical neurons. TNF-expressing neurons from TNF-transgenic mice were found to be strongly protected from glutamate-induced apoptosis. Neurons from wild type and TNFR1(-/-) mice prestimulated with TNF or agonistic TNFR2-specific antibodies were also resistant to excitotoxicity, whereas TNFR2(-/-) neurons died upon glutamate and/or TNF exposures. Both protein kinase B/Akt and nuclear factor-kappa B (NF-kappa B) activation were apparent upon TNF treatment. Both TNFR1 and TNFR2 induced the NF-kappa B pathway, yet with distinguishable kinetics and upstream activating components, TNFR1 only induced transient NF-kappa B activation, whereas TNFR2 facilitated long term phosphatidylinositol 3-kinase-dependent NF-kappa B activation strictly. Glutamate-induced triggering of the ionotropic N-methyl-D-aspartate receptor was required for the enhanced and persistent phosphatidylinositol 3-kinase-dependent NF-kappa B activation by TNFR2, indicating a positive cooperation of TNF and neurotransmitter-induced signal pathways. TNFR2-induced persistent NF-kappa B activity was essential for neuronal survival. Thus, the duration of NF-kappa B activation is a critical determinant for sensitivity toward excitotoxic stress and is dependent on a differential upstream signal pathway usage of the two TNFRs.

Authors+Show Affiliations

Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, D-70569 Stuttgart, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15155767

Citation

Marchetti, Lara, et al. "Tumor Necrosis Factor (TNF)-mediated Neuroprotection Against Glutamate-induced Excitotoxicity Is Enhanced By N-methyl-D-aspartate Receptor Activation. Essential Role of a TNF Receptor 2-mediated Phosphatidylinositol 3-kinase-dependent NF-kappa B Pathway." The Journal of Biological Chemistry, vol. 279, no. 31, 2004, pp. 32869-81.
Marchetti L, Klein M, Schlett K, et al. Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway. J Biol Chem. 2004;279(31):32869-81.
Marchetti, L., Klein, M., Schlett, K., Pfizenmaier, K., & Eisel, U. L. (2004). Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway. The Journal of Biological Chemistry, 279(31), 32869-81.
Marchetti L, et al. Tumor Necrosis Factor (TNF)-mediated Neuroprotection Against Glutamate-induced Excitotoxicity Is Enhanced By N-methyl-D-aspartate Receptor Activation. Essential Role of a TNF Receptor 2-mediated Phosphatidylinositol 3-kinase-dependent NF-kappa B Pathway. J Biol Chem. 2004 Jul 30;279(31):32869-81. PubMed PMID: 15155767.
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TY - JOUR T1 - Tumor necrosis factor (TNF)-mediated neuroprotection against glutamate-induced excitotoxicity is enhanced by N-methyl-D-aspartate receptor activation. Essential role of a TNF receptor 2-mediated phosphatidylinositol 3-kinase-dependent NF-kappa B pathway. AU - Marchetti,Lara, AU - Klein,Matthias, AU - Schlett,Katalin, AU - Pfizenmaier,Klaus, AU - Eisel,Ulrich L M, Y1 - 2004/05/21/ PY - 2004/5/25/pubmed PY - 2004/9/11/medline PY - 2004/5/25/entrez SP - 32869 EP - 81 JF - The Journal of biological chemistry JO - J Biol Chem VL - 279 IS - 31 N2 - We have previously shown that two tumor necrosis factor (TNF) receptors (TNFR) exhibit antagonistic functions during neurodegenerative processes in vivo with TNFR1 aggravating and TNFR2 reducing neuronal cell loss, respectively. To elucidate the neuroprotective signaling pathways of TNFR2, we investigated glutamate-induced excitotoxicity in primary cortical neurons. TNF-expressing neurons from TNF-transgenic mice were found to be strongly protected from glutamate-induced apoptosis. Neurons from wild type and TNFR1(-/-) mice prestimulated with TNF or agonistic TNFR2-specific antibodies were also resistant to excitotoxicity, whereas TNFR2(-/-) neurons died upon glutamate and/or TNF exposures. Both protein kinase B/Akt and nuclear factor-kappa B (NF-kappa B) activation were apparent upon TNF treatment. Both TNFR1 and TNFR2 induced the NF-kappa B pathway, yet with distinguishable kinetics and upstream activating components, TNFR1 only induced transient NF-kappa B activation, whereas TNFR2 facilitated long term phosphatidylinositol 3-kinase-dependent NF-kappa B activation strictly. Glutamate-induced triggering of the ionotropic N-methyl-D-aspartate receptor was required for the enhanced and persistent phosphatidylinositol 3-kinase-dependent NF-kappa B activation by TNFR2, indicating a positive cooperation of TNF and neurotransmitter-induced signal pathways. TNFR2-induced persistent NF-kappa B activity was essential for neuronal survival. Thus, the duration of NF-kappa B activation is a critical determinant for sensitivity toward excitotoxic stress and is dependent on a differential upstream signal pathway usage of the two TNFRs. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15155767/Tumor_necrosis_factor__TNF__mediated_neuroprotection_against_glutamate_induced_excitotoxicity_is_enhanced_by_N_methyl_D_aspartate_receptor_activation__Essential_role_of_a_TNF_receptor_2_mediated_phosphatidylinositol_3_kinase_dependent_NF_kappa_B_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)77588-5 DB - PRIME DP - Unbound Medicine ER -