Neuroprotective effect of apolipoprotein E against ischemia.
Apolipoprotein E (APOE) deficiency has been shown to worsen neuronal injuries after cerebral ischemia. However, the molecular mechanism underlying the protective effect of APOE remains uncertain, even though several mechanisms including excitotoxicity, free radicals, and apoptosis have been cited as causes of selective neuronal vulnerability in cerebral ischemia. In the present study, we compared the vulnerability of cultured neurons prepared from APOE-knockout mice upon exposure to glutamate, hydrogen peroxide, and staurosporine. No significant difference in cell viability was observed after exposure to glutamate or staurosporine between APOE-deficient and wild-type mice. However, exposure to hydrogen peroxide significantly increased the level of cell death in APOE-deficient mice compared with that in wild-type mice. In the adult mice, after transient forebrain ischemia for 12 min, APOE-deficient mice showed more neuronal death than wild-type mice. Pretreatment of APOE-deficient mice with vitamin E for 2 months markedly reduced neuronal death caused by ischemia. The results suggested that APOE exerted the neuroprotective effect against ischemia through its antioxidant action, but not through mitigation of glutamate toxicity or blocking of apoptosis.
Kitagawa
Kazuo
K
Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine (A8), 2-2 Yamadaoka, Suita-city, Osaka 565-0871, Japan. kitagawa@medone.med.osaka-u.ac.jp
Matsumoto
Masayasu
M
Hori
Masatsugu
M
Yanagihara
Takehiko
T
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D019311:Staurosporine / Q000494:pharmacology
D001057:Apolipoproteins E; D018696:Neuroprotective Agents; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D019311:Staurosporine