Divergence of brain prostaglandin H synthase activity and oxidative damage in mice with encephalitis.

Valyi-Nagy T, Sidell KR, Marnett LJ, Roberts LJ, Dermody TS, Morrow JD, Montine TJ
J Neuropathol Exp Neurol. 1999 58 (12): 1269-75

PMID: 10604752 · DOI:10.1097/00005072-199912000-00008

Several lines of evidence point to inflammation and increased oxidant injury in brain regions of patients with Alzheimer disease (AD). Prostaglandin H synthase (PGHS) catalyzes the limiting step in prostaglandin synthesis and generates a potent oxidizing agent as by-product. One form of PGHS, PGHS-2, is induced by pro-inflammatory signals; thus leading to the 2-step hypothesis that pro-inflammatory signals in AD brain induce PGHS-2 that in turn contributes to brain oxidant injury. Here we have tested directly this 2-step hypothesis in a murine reovirus type 3 encephalitis model by measuring cerebral PGHS activity and quantifying oxidant injury. Our results showed a robust chronic inflammatory infiltrate and a 2-fold increase in PGHS activity in encephalitic mice compared with controls. Despite these changes, there was no significant increase in F2-isoprostanes or F4-neuroprostanes, accurate in vivo biomarkers of oxidant injury, and only minimal accumulation of protein adducts from the lipid peroxidation product 4-hydroxy-2-nonenal in the most intensely inflamed brain regions. These results challenge the proposal of others that pro-inflammatory induction of PGHS activity significantly contributes to oxidant injury in brain.

MeSH Terms (12)

Aldehydes Animals Brain Cell Line Encephalitis, Viral Immunohistochemistry In Situ Nick-End Labeling Lipid Peroxides Mice Oxidation-Reduction Prostaglandin-Endoperoxide Synthases Reoviridae Infections

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