Lack of quinone reductase activity suggests that amyloid-β peptide/ERAB induced lipid peroxidation is not directly related to production of reactive oxygen species by redoxcycling

Abstract

Mitochondrial type II hydroxyacyl-CoA dehydrogenase (ERAB) has recently been shown to mediate amyloid-β peptide (Aβ) induced apoptosis and neurodegeneration. The precise mechanism of cell death induction is unknown, however, Aβ inhibits ERAB activities and as a result of ERAB-Aβ interactions, enhanced formation of lipid peroxidation products occur. The possibility that ERAB mediates quinone reduction is therefore investigated, thus giving the potential of redoxcycling and production of reactive oxygen species, leading to lipid peroxidation. Recombinant human ERAB was produced in a bacterial expression system and enzymological properties were evaluated. Using several orthoquinones as substrates, no ERAB mediated quinone reductase activity was found either in the presence or absence of Aβ, suggesting that the observed in vivo lipid peroxidation is a result of other mechanisms than redoxcycling by quinones.