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Neuronal oxidative damage from activated innate immunity is EP2 receptor-dependent.
J Neurochem 2002; 83(2):463-70JN

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.

Authors+Show Affiliations

Department of Pathology, Vanderbilt University, Nashville, Tennessee, USA. tmontine@u.washington.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -