Apolipoprotein D modulates F2-isoprostane and 7-ketocholesterol formation and has a neuroprotective effect on organotypic hippocampal cultures after kainate-induced excitotoxic injury.
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 microg/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.
Department of Anatomy, Beijing University of Chinese Medicine, Beijing 100029, China.
Xin
X
He
Jinatta
J
Jittiwat
Ji-Hyun
JH
Kim
Andrew M
AM
Jenner
Akhlaq A
AA
Farooqui
Shutish C
SC
Patel
Wei-Yi
WY
Ong
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D053399:Apolipoproteins D / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism; D028441:F2-Isoprostanes / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007608:Kainic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D007653:Ketocholesterols / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009924:Organ Culture Techniques; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000447:Aldehydes; D053399:Apolipoproteins D; D028441:F2-Isoprostanes; D007653:Ketocholesterols; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D016718:Arachidonic Acid; D002784:Cholesterol; D007770:L-Lactate Dehydrogenase; C027576:4-hydroxy-2-nonenal; C003001:7-ketocholesterol; D007608:Kainic Acid