Vitamin E prevents the neuronal cell death by repressing cyclooxygenase-2 activity.
The accumulation of damage caused by oxidative stress exacerbates cell death in many neurodegenerative diseases. We evaluated the mechanism of neuronal cell death raised by glutamate-induced toxicity, using the immortalized mouse hippocampal cell line HT-22. Our results showed that vitamin E prevented glutamate-induced cell death, accompanied by the decline of cyclooxygenase-2 expression confirmed by reverse transcriptase polymerase chain reaction and immunocytochemistry. Moreover, the neuroprotection was still effective even when vitamin E was supplied after glutamate treatment. The decline of cyclooxygenase-2 activity was also highly correlated with the neural protective effect against glutamate-induced toxicity. These results represent new insights about the timing of vitamin E supplementation after toxic stimulation and one mechanism by which vitamin E could prevent neuronal cell death by controlling cyclooxygenase-2 activity.
Ezaki
Yasuyuki
Y
Division of Neurobiology and Behavior, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. kazuyuki@net.nagasaki-u.ac.jp
Nishihara
Eijun
E
Shibata
Yoshisada
Y
Matsuo
Takayuki
T
Kitagawa
Naoki
N
Nagata
Izumi
I
Shinohara
Kazuyuki
K
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D014810:Vitamin E; D018698:Glutamic Acid; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases