title: Edaravone protects cortical neurons from apoptosis by inhibiting the translocation of BAX and Increasing the interaction between 14-3-3 and p-BAD.
abstract: Edaravone, a free radical scavenger, has shown neuroprotection properties in both animals and humans. To evaluate the mechanisms involved, we obtained a culture of almost pure neurons. The neurons, either untreated or prophylactically treated with edaravone, were exposed to 300 μM hydrogen peroxide. We examined alterations in mitochondria, the percent of apoptotic cells and the immunoblots of key regulatory proteins, and the protein-protein interactions and the cellular locations of cytochrome c. The levels of p-JNK (Thr183/Tyr185) and cytochrome c in cytosol and BAX in heavy membrane (HM), respectively, were increased at 0.5 h and reached the peak at 12 h after stimulation with hydrogen peroxide. The levels of p-BAD and BAX in the cytosol and the interaction between BAD and 14-3-3 were decreased in the untreated neurons. However, edaravone could prevent these changes. In addition, mitochondrial morphology was better preserved and the percentage of apoptosis was lower under the treatment with edaravone. In summary, the present study indicates that edaravone could protect neurons by inhibiting: (1) the activity of JNK, (2) the disassociation of BAD from 14-3-3, and (3) the translocation of BAX from cytosol to mitochondria.
authors: The First Affiliated Hospital of Nanjing Medical University,   Jiangsu,   China.
authors: Jin
authors: J
authors: Fan
authors: Ning
authors: N
authors: Zhang
authors: Guoyong
authors: G
authors: Yin
authors: Zitao
authors: Z
authors: Zhang
authors: Gang
authors: G
authors: Cheng
authors: Wenwu
authors: W
authors: Qian
authors: Hao
authors: H
authors: Long
authors: Weihua
authors: W
authors: Cai
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D000077553:Edaravone; D005260:Female; D005333:Fetus / Q000166:cytology; D016166:Free Radical Scavengers / Q000494:pharmacology; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018696:Neuroprotective Agents / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism*; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; C494821:Bad protein, rat; C494828:Bax protein, rat; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D000077553:Edaravone; D000983:Antipyrine