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

Abstract

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.