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

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Abstract
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.