Apolipoprotein D modulates F-2-isoprostane and 7-ketocholesterol formation and has a neuroprotective effect on organotypic hippocampal cultures after kainate-induced excitotoxic injury

作者：He Xin; Jittiwat Jinatta; Kim Ji Hyun; Jenner Andrew M; Farooqui Akhlaq A; Patel Shutish C^*; Ong Wei Yi

来源：Neuroscience Letters, 2009, 455(3): 183-186.

DOI：10.1016/j.neulet.2009.03.038

• Apolipoprotein D
• Oxidative stress
• Lipid peroxidation
• Oxysterols
• 7-Ketocholesterol
• Excitotoxicity

Apolipoprotein D (apoD), a member of the lipocalin family of transporter proteins binds a number of small lipophilic molecules including arachidonic acid and cholesterol. Recent studies showed a protective function of mammalian apoD as well as its insect and plant homologs against oxidative stress. In this study we investigated the effect of direct addition of exogenous human apoD protein purified from breast cystic fluid to rat hippocampal slice cultures after excitotoxic injury induced by the glutamate analog kainate. ApoD at a concentration of 10 mu g/ml partially prevented loss of MAP2 immunostaining and LDH release from injured hippocampal neurons after kainate injury. ApoD also attenuated the increase in oxidative products of arachidonic acid and cholesterol, F-2-isoprostanes and 7-ketocholesterol, respectively, after kainate treatment. In view of the molecular structure of apoD which consists of an eight stranded beta barrel that forms a binding pocket for a number of small hydrophobic molecules, we propose that apoD promotes its neuroprotective effects by binding to arachidonic acid and cholesterol thus preventing their oxidation to neurotoxic products such as 4-hydroxynonenal (4-HNE) and 7-ketocholesterol.

• 出版日期2009-5-22
• 单位北京中医药大学