Increased Copper-Mediated Oxidation of Membrane Phosphatidylethanolamine in Autism

We have previously reported that levels of phosphatidylethanolamine (PE) in the erythrocyte membrane and of ceruloplasmin, a copper-transport antioxidant protein, in the serum are lower in children with autism than in control subjects. In the present study, we report that (a) copper oxidizes and reduces the levels of membrane PE and (b) copper-mediated oxidation of PE is higher in lymphoblasts from autistic subjects than from control subjects. The effect of copper was examined on the oxidation of liposomes composed of brain lipids from mice and also on the lymphoblasts from autism and control subjects. Among the various metal cations (copper, iron, calcium, cadmium and zinc), only copper was found to oxidize and decrease the levels of PE. The metal cations did not affect the levels of other phospholipids. The action of copper on PE oxidation was time-dependent and concentration-dependent. No difference was observed between copper-mediated oxidation of diacylPE and alkenyl-PE (plasmalogen), suggesting that plasmalogenic and non-plasmalogenic PE are equally oxidized by copper. Together, these studies suggest that ceruloplasmin and copper may contribute to oxidative stress and to reduced levels of membrane PE in autism.