Apolipoprotein E deletion has no effect on copper-induced oxidative stress in the mice brain

The current study was designed to investigate effect of copper administration on oxidative damage to the brain in ApoE^-/- mice and to explore the putative neuroprotective effects rendered by apolipoprotein E (ApoE). Male C57BL/6 ApoE^-/- and wild-type mice were randomly assigned into four groups, ApoE mice wild-type mice treated with either copper or saline. Copper sulphate pentahydrate or saline (200 µl) were administered intragastrically daily for 12 weeks. Expression of malondialdehyde, superoxide dismutase (SOD), hemeoxygenase 1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1) were determined by a combination of biochemical assays. The concentration of copper in the brain of C57BL/6 mice and ApoE mice treated by copper significantly increased compared with mice treated by saline (P=0.0099 and P=0.0443). Compared with the C57BL/6 mice treated by copper, the level of the ApoE mice treated by copper was higher (P=0.018). TBARS and SOD activities or the expressions of NQO1 and HO-1 in the brain were not significantly different amongst the four experimental groups of mice. The relative value of NQO1/β-actin expression in the brain of the ApoE^-/- mice was similar in both saline and copper administration experimental groups. However, Western blot analysis showed that NQO1 expression was significantly higher in the ApoE mice brain treated with saline compared with saline treated wild-type mice (P=0.0449). ApoE does not function in protecting the brain from oxidative damage resulting from copper build-up in Wilson's disease, but may play a role in regulating copper accumulation in the brain.