Protective effect of apolipoprotein E against ischemic neuronal injury is mediated through antioxidant action.
Recent studies have demonstrated that apolipoprotein E (APOE) deficiency worsened neuronal injuries after transient focal and global cerebral ischemia. However, the molecular mechanism underlying the protective effect of APOE remains uncertain, even though several mechanisms, including excitotoxicty, free radicals, and apoptosis, have been cited as causes of selective neuronal vulnerability in cerebral ischemia. In the present study, we first 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. 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 suggest that APOE exerted its 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, Departement 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
Kuwabara
Keisuke
K
Takasawa
Ken-Ichiro
K
Tanaka
Shigeru
S
Sasaki
Tsutomu
T
Matsushita
Kohji
K
Ohtsuki
Toshiho
T
Yanagihara
Takehiko
T
Hori
Masatsugu
M
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000502:physiology*; D018698:Glutamic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D016548:Prosencephalon / Q000098:blood supply; D019311:Staurosporine / Q000494:pharmacology; D014810:Vitamin E / Q000494:pharmacology
D000975:Antioxidants; D001057:Apolipoproteins E; D014810:Vitamin E; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D019311:Staurosporine