Lipid peroxidation and 4-hydroxy-2-nonenal formation by copper ion bound to amyloid-β peptide

Abstract

Abstract-The lipid peroxidation product 4-hydroxy-2-nonenal (HNE) is proposed to be a toxic factor in the pathogenesis of Alzheimer's disease. The primary products of lipid peroxidation are phospholipid hydroperoxides and degraded reactive aldehydes, such as HNE, as secondary peroxidation products. In this study, we investigated the role of amyloid-β peptide (Aβ) in the formation of phospholipid hydroperoxides and HNE by copper ion bound to Aβ. The Aβ 1-42 -Cu 2+ (1:1 molar ratio) complex showed an activity to form phospholipid hydroperoxides from phospholipid, 1-palmitoyl-2-linoleoyl phosphatidylcholine (PLPC), through Cu 2+ reduction in the presence of ascorbic acid. The phospholipid hydroperoxides were considered to be racemic mixture of 9-hydroperoxide and 13-hydroperoxide of linoleoyl residue. When Cu 2+ was bound to two molar equivalents of Aβ 1-42 (2 Aβ 1-42 -Cu 2+ ), lipid peroxidation was inhibited.

Simvastatin Protects against Amyloid β and HIV-1 Tat-Induced Promoter Activities of Inflammatory Genes in Brain Endothelial Cells

“…Indeed, pro-oxidative/antioxidative effects of A␤ can be regulated by the molar ratio of A␤ to Cu 2ϩ . When Cu 2ϩ is bound to two molar equivalents of A␤, lipid peroxidation is inhibited and A␤ exerts antioxidant effects (Hayashi et al, 2007). Thus, it is possible that these finely tuned regulations of cellular redox balance might be responsible for the lack of CCL-2 stimulation by 1 M A␤.…”

Nucleic acid oxidation in Alzheimer disease

“…Interestingly, the levels of 8OHG are inversely related to the amount of amyloid-β present as extracellular deposits [10] or intracellular oligomeric forms [58], suggesting a complex interplay between amyloid-β and redox metal activity that may be critical to metal dynamics within the neuronal cytoplasm [59,60]. A possible key element in these dynamics is mitochondria in the neuronal cell body.…”

Copper and Copper-Containing Pesticides: Metabolism, Toxicity and Oxidative Stress

“…Many researchers found adverse effects both in vivo and in vitro of Cu overload [5,25,33,62]. Copper injection demonstrated the modification of activities of antioxidant enzymes.…”

“…This has been manifested as increased production of pentane and hepatic malondialdehyde when liver homogenates or hepatocytes are exposed to ionic copper. Moreover, dietary copper overload in rats resulted in in vivo peroxidation of mitochondrial membrane lipids demontstrated by increased concentrations of conjugated dienes and thiobarbituric acid-reacting substances (TBARS) [25,58]. Copper-catalyzed lipid peroxidation also appears to underlie the alterations in hepatocyte lysosomes in copper-loaded rats [45].…”