Apolipoprotein D modulates F2-isoprostane and 7-ketocholesterol formation and has a neuroprotective effect on organotypic hippocampal cultures after kainate-induced excitotoxic injury

NEUROSCIENCE LETTERS

卷:455

Article

He, Xin²  Jittiwat, Jinatta³  Kim, Ji-Hyun³  Jenner, Andrew M.^4,5  Farooqui, Akhlaq A.⁶  Patel, Shutish C.^1,7  Ong, Wei-Yi^3,5 

[1] New England Biomed Res Ctr, Neurobiol Res Lab, Newington, CT 06111 USA

[2] Beijing Univ Chinese Med, Dept Anat, Beijing 100029, Peoples R China

[3] Natl Univ Singapore, Dept Anat, Singapore 119260, Singapore

[4] Natl Univ Singapore, Dept Biochem, Singapore 119260, Singapore

[5] Natl Univ Singapore, Ageing Neurobiol Res Programme, Singapore 119260, Singapore

[6] Ohio State Univ, Dept Med Biochem, Columbus, OH 43210 USA

[7] VA Connecticut Healthcare Syst, Newington, CT 06111 USA

关键词: Apolipoprotein D;    Oxidative stress;    Lipid peroxidation;    Oxysterols;    7-Ketocholesterol;    Excitotoxicity;   

DOI  :  10.1016/j.neulet.2009.03.038

来源: Elsevier

【 摘 要 】

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. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

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