Lack of quinone reductase activity suggests that amyloid-beta peptide/ERAB induced lipid peroxidation is not directly related to production of reactive oxygen species by redoxcycling.
Mitochondrial type II hydroxyacyl-CoA dehydrogenase (ERAB) has recently been shown to mediate amyloid-beta peptide (Abeta) induced apoptosis and neurodegeneration. The precise mechanism of cell death induction is unknown, however, Abeta inhibits ERAB activities and as a result of ERAB-Abeta 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 Abeta, suggesting that the observed in vivo lipid peroxidation is a result of other mechanisms than redoxcycling by quinones.
Salim
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Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77, Stockholm, Sweden.
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Mårtensson
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Oppermann
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D015094:3-Hydroxyacyl CoA Dehydrogenases; D000214:Acyl Coenzyme A / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007700:Kinetics; D015227:Lipid Peroxidation / Q000502:physiology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013379:Substrate Specificity; D015262:Xenobiotics / Q000378:metabolism
D000214:Acyl Coenzyme A; D016229:Amyloid beta-Peptides; D002352:Carrier Proteins; D017382:Reactive Oxygen Species; D015262:Xenobiotics; C010667:acetoacetyl CoA; C030372:3-hydroxybutyryl-coenzyme A; D015094:3-Hydroxyacyl CoA Dehydrogenases; C108634:HSD17B10 protein, human; C458480:Hsd17b10 protein, mouse; D016660:NAD(P)H Dehydrogenase (Quinone)