Generation of reactive oxygen species accounts for cytotoxicity of an endogenous dopaminergic neurotoxin, (R)-N-methylsalsolinol, to differentiated dopaminergic SH-SY5Y cells.
The mechanism of the cytotoxicity of endogenous dopamine-derived (R)-1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [(R)-N-methylsalsolinol] to differentiated human dopaminergic neuroblastoma SH-SY5Y cells was studied using a reduction-oxidation indicator, Alamar Blue. N-Methylsalsolinol and its oxidation product, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, were found to inhibit oxidative phosphorylation, as shown by the Redox capacity. Antioxidants, such as reduced glutathione, catalase, Tris and n-propyl gallate, reduced the cytotoxicity of N-methylsalsolinol, suggesting that hydroxyl radical was the major reactive oxygen species for the cytotoxicity. Deprenyl also protected the cells from the decrease of the Redox capavity by N-methylsalsolinol. However, antioxidants did not protect the cells from the cytotoxicity of the catechol isoquinolinium ion. The results suggest that oxidative stress induced by hydroxyl radical may be involved in the cell death of dopaminergic neurons by N-methylsalsolinol.
Department of Applied Chemistry, Nagoya Institute of Technology, Japan.
C
C
Minami
Y
Y
Deng
W
W
Maruyama
T
T
Takahashi
M
M
Kawai
D
D
Nakahara
M
M
Naoi
D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D009447:Neuroblastoma; D009498:Neurotoxins / Q000633:toxicity*; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012490:Salsoline Alkaloids / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured
D007546:Isoquinolines; D009498:Neurotoxins; D017382:Reactive Oxygen Species; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; D017665:Hydroxyl Radical; C032837:salsoline; C039109:isoquinoline; D004298:Dopamine