ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Abstract: Oxidative stress is implicated in the pathogenesis ofexperimental allergic encephalomyelitis (EAE), a model for multiple sclerosis.Heme oxygenase-1 (HO-1) is a heat shock protein induced by oxidative stress.HO-1 metabolizes the pro-oxidant heme to the antioxidant biliverdin and CO.HO-1 requires electrons, donated by NADPH cytochrome P450 reductase(henceforth, reductase), for catalytic activity. EAE was induced with apeptide of proteolipid protein in SJL mice, and the expression of HO-1 andreductase in the hindbrain was analyzed. HO-1 protein levels weresignificantly increased in EAE animals compared with control mice. HO-1expression was present in ameboid macrophages, reactive microglia, andastrocytes in white matter tracks. Bergmann glia and ameboid macrophages alsowere occasionally stained in the molecular layer of the cerebellum. UnlikeHO-1, reductase protein levels decreased with disease severity. HO-1 andreductase were associated with each other in endoplasmic reticulum micelles,suggesting that the decrease in reductase does not interfere with itsassociation with HO-1. In cells that express HO-1, the association ofreductase with HO-1 should competitively inhibit the interaction of reductasewith cytochrome P450 isozymes and thereby limit free radical production as thelatter two enzymes act cooperatively to produce superoxide. The increase inHO-1 together with the decrease in reductase may be part of a common defensemechanism attempting to minimize tissue damage in several neurologicalconditions.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0752555.x
