Edaravone improves the expression of nerve growth factor in human astrocytes subjected to hypoxia/reoxygenation.
Edaravone (MCI-186, 3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, is known to ameliorate postischemic neuronal dysfunction. Nerve growth factor (NGF) is essential for neuronal growth and survival. We have addressed the effect of edaravone on the NGF expression in astrocytes exposed to hypoxia/reoxygenation. Normal human astrocytes in culture were incubated under hypoxia for 3h and then treated with edaravone under normal culture condition for up to 72h. The levels of NGF mRNA were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) or real-time quantitative PCR and NGF protein levels were measured by enzyme-linked immunosorbent assay (ELISA). Edaravone enhanced, in time- and concentration-dependent manners, the expressions of NGF mRNA and protein in astrocytes under reoxygenation condition. After the treatment for 72h, 1mmol/L edaravone enhanced the levels of NGF protein in astrocyte-conditioned media by 1.7-fold of the control. An inhibitor of c-Jun N-terminal kinase (JNK) suppressed the effect of edaravone on the NGF expression, and cellular levels of phospho-JNK were increased in response to edaravone. We conclude that edaravone enhances, via the JNK pathway, NGF expression in astrocytes. This agent may exert a neurotrophic effect in the therapy of brain injury in ischemia/reperfusion.
Yoshida
Hidemi
H
Department of Vascular Biology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Zaifu-cho, Hirosaki, Japan. hidemi_yoshida@gakushikai.jp
Metoki
Norifumi
N
Ishikawa
Akira
A
Imaizumi
Tadaatsu
T
Matsumiya
Tomoh
T
Tanji
Kunikazu
K
Ota
Ken
K
Ohyama
Chikara
C
Satoh
Kei
K
D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism*; D015153:Blotting, Western; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020932:Nerve Growth Factor / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D048031:JNK Mitogen-Activated Protein Kinases; D000077553:Edaravone; D010100:Oxygen; D000983:Antipyrine