Tags

Type your tag names separated by a space and hit enter

Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent.

Abstract

Increase in prostaglandin (PG) E2 levels and oxidative damage are associated with diseases of brain that involve activation of innate immunity. We tested the hypothesis that cerebral oxidative damage resulting from activation of innate immunity with intracerebroventricular (icv) lipopolysaccharide (LPS) is dependent on PGE2-mediated signaling. We measured two quantitative in vivo biomarkers of lipid peroxidation: F2-isoprostanes (IsoPs) that derive from arachidonic acid (AA) that is uniformly distributed in all cell types in brain, and F4-neuroprostanes (NeuroPs) that derive from docosahexaenoic acid (DHA) that is highly concentrated in neuronal membranes. LPS stimulated delayed elevations in cerebral F2-IsoPs and F4-NeuroPs that were completely suppressed by indomethacin or ibuprofen pre-treatment. LPS-induced cerebral oxidative damage was abolished by disruption of subtype 2 receptor for PGE2 (EP2). In contrast, initial oxidative damage from icv kainic acid (KA) was more rapid than with LPS also was completely suppressed by indomethacin or ibuprofen pre-treatment but was independent of EP2 receptor activation. The protective effect of deleting the EP2 receptor was not associated with changes in cerebral eicosaniod production, but was partially related to reduced induction of nitric oxide synthase (NOS) activity. These results suggest the EP2 receptor as a therapeutic target to limit oxidative damage from activation of innate immunity in cerebrum.

Links

  • FREE Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Pathology, Vanderbilt University, Nashville, Tennessee, USA. tmontine@u.washington.edu

    , , , ,

    Source

    Journal of neurochemistry 83:2 2002 Oct pg 463-70

    MeSH

    Animals
    Anti-Inflammatory Agents, Non-Steroidal
    Autoimmune Diseases of the Nervous System
    Biomarkers
    Brain Chemistry
    Citrulline
    Disease Models, Animal
    Docosahexaenoic Acids
    F2-Isoprostanes
    Immunity, Innate
    Isoprostanes
    Kainic Acid
    Lipid Peroxidation
    Lipopolysaccharides
    Male
    Mice
    Mice, Inbred BALB C
    Mice, Inbred C57BL
    Mice, Knockout
    Neurons
    Oxidation-Reduction
    Oxidative Stress
    Receptors, Prostaglandin E
    Receptors, Prostaglandin E, EP2 Subtype

    Pub Type(s)

    Comparative Study
    Journal Article
    Research Support, U.S. Gov't, P.H.S.

    Language

    eng

    PubMed ID

    12423256

    Citation

    Montine, Thomas J., et al. "Neuronal Oxidative Damage From Activated Innate Immunity Is EP2 Receptor-dependent." Journal of Neurochemistry, vol. 83, no. 2, 2002, pp. 463-70.
    Montine TJ, Milatovic D, Gupta RC, et al. Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent. J Neurochem. 2002;83(2):463-70.
    Montine, T. J., Milatovic, D., Gupta, R. C., Valyi-Nagy, T., Morrow, J. D., & Breyer, R. M. (2002). Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent. Journal of Neurochemistry, 83(2), pp. 463-70.
    Montine TJ, et al. Neuronal Oxidative Damage From Activated Innate Immunity Is EP2 Receptor-dependent. J Neurochem. 2002;83(2):463-70. PubMed PMID: 12423256.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent. AU - Montine,Thomas J, AU - Milatovic,Dejan, AU - Gupta,Ramesh C, AU - Valyi-Nagy,Tibor, AU - Morrow,Jason D, AU - Breyer,Richard M, PY - 2002/11/9/pubmed PY - 2002/11/26/medline PY - 2002/11/9/entrez SP - 463 EP - 70 JF - Journal of neurochemistry JO - J. Neurochem. VL - 83 IS - 2 N2 - Increase in prostaglandin (PG) E2 levels and oxidative damage are associated with diseases of brain that involve activation of innate immunity. We tested the hypothesis that cerebral oxidative damage resulting from activation of innate immunity with intracerebroventricular (icv) lipopolysaccharide (LPS) is dependent on PGE2-mediated signaling. We measured two quantitative in vivo biomarkers of lipid peroxidation: F2-isoprostanes (IsoPs) that derive from arachidonic acid (AA) that is uniformly distributed in all cell types in brain, and F4-neuroprostanes (NeuroPs) that derive from docosahexaenoic acid (DHA) that is highly concentrated in neuronal membranes. LPS stimulated delayed elevations in cerebral F2-IsoPs and F4-NeuroPs that were completely suppressed by indomethacin or ibuprofen pre-treatment. LPS-induced cerebral oxidative damage was abolished by disruption of subtype 2 receptor for PGE2 (EP2). In contrast, initial oxidative damage from icv kainic acid (KA) was more rapid than with LPS also was completely suppressed by indomethacin or ibuprofen pre-treatment but was independent of EP2 receptor activation. The protective effect of deleting the EP2 receptor was not associated with changes in cerebral eicosaniod production, but was partially related to reduced induction of nitric oxide synthase (NOS) activity. These results suggest the EP2 receptor as a therapeutic target to limit oxidative damage from activation of innate immunity in cerebrum. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/12423256/Neuronal_oxidative_damage_from_activated_innate_immunity_is_EP2_receptor_dependent_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2002&volume=83&issue=2&spage=463 DB - PRIME DP - Unbound Medicine ER -