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

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.