Edaravone protects against MPP+ -induced cytotoxicity in rat primary cultured astrocytes via inhibition of mitochondrial apoptotic pathway.
Edaravone (Eda) is a potent scavenger of hydroxyl radicals and has been demonstrated to be beneficial for patients with acute ischemic stroke. This study was set out to investigate whether Eda protect against MPP(+)-induced cytotoxicity in rat primary cultured astrocytes. The results showed that pre-treatment with Eda inhibited astrocytic apoptosis and lactate dehydrogenase release induced by MPP(+) (200 microM). Further study revealed that Eda prevented GSH depletion, down-regulated mRNA expressions of NADPH oxidase membrane subunit gp91 and membrane-translocated subunit p47, and prevented the decreases of state 3 respiration respiration and respiratory control ratio induced by MPP(+), and thereby inhibited reactive oxygen species production evoked by MPP(+). Moreover, Eda could ameliorate mitochondrial respiratory function, restrain, and prevent mitochondrial membrane potential loss induced by MPP(+). Consequently, Eda inhibited releases of cytochrome c and apoptosis-inducing factor induced by MPP(+). Taken together, these findings reveal for the first time that Eda protects against MPP(+)-induced astrocytic apoptosis via decreasing intracellular reactive oxygen species level and subsequently inhibiting mitochondrial apoptotic pathway. The antiapoptosis effects of Eda on astrocytes may provide a new perspective on neuroprotective therapy.
Chen
Hui
H
Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu, China.
Wang
Sen
S
Ding
Jian-Hua
JH
Hu
Gang
G
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects* / Q000502:physiology; D000077553:Edaravone; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D015655:1-Methyl-4-phenylpyridinium; D000077553:Edaravone; D000983:Antipyrine