Glutathione S-transferase Pi is a dopamine-inducible suppressor of dopamine-induced apoptosis in PC12 cells

被引:27
作者
Ishisaki, A [1 ]
Hayashi, H [1 ]
Suzuki, S [1 ]
Ozawa, K [1 ]
Mizukoshi, E [1 ]
Miyakawa, K [1 ]
Suzuki, M [1 ]
Imamura, T [1 ]
机构
[1] Natl Inst Adv Ind Sci & Technol, Gene Discovery Res Ctr, AIST, Tsukuba, Ibaraki 3058566, Japan
关键词
apoptosis; dopamine; FGF-1; glutathione S-transferase class Pi; Jun-N-terminal kinase; PC12; cells;
D O I
10.1046/j.1471-4159.2001.00351.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The finding that the neurotransmitter dopamine induces apoptosis in neurons implies the existence of a cellular mechanism by which dopaminergic neurons protect themselves from dopamine-induced apoptosis. By profiling the expression of a number of genes in differentiating PC12 cells which exhibit elevated levels of dopamine biosynthesis,we found that expression of glutathione S-transferase class Pi (GSTp) mRNA was selectively up-regulated. Interestingly, dopamine added to the culture medium of PC12 cells also augmented their expression of GSTp mRNA. Suppression of GSTp expression by transfection of its antisense expression vector augmented dopamine-induced apoptosis of PC12 cells. Conversely, overexpression of GSTp made the resultant PC12 transfectants highly resistant to dopamine-induced apoptosis. Transfection of the antisense or sense GSTp expression vectors also resulted in corresponding augmentation or suppression of dopamine-induced activation of cell-associated Jun-N-terminal kinase (JNK), which has been suggested to mediate dopamine-induced apoptosis in neuronal cells. These results indicate that GSTp is a dopamine-inducible suppressor of dopamine-induced apoptosis in PC12 cells, and suggest that this activity is exerted through inhibition of JNK activity.
引用
收藏
页码:1362 / 1371
页数:10
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