DT-diaphorase Protects Astrocytes from Aminochrome-induced Toxicity

Astrocytes are exposed to aminochrome via the oxidation of dopamine that is taken up from the synaptic cleft after its release from dopaminergic neurons. Glutathione transferase M2-2 (GSTM2) has been shown to protect astrocytes from aminochrome-induced toxicity, but astrocytes also express DT-diaphorase, which has been shown to prevent aminochrome-induced neurotoxicity in dopaminergic neurons. Therefore, the question is whether DT-diaphorase also protects astrocytes from aminochrome-induced toxicity. DT-diaphorase is constitutively expressed in U373MG cells, and its inhibition by dicoumarol induced a significant increase of aminochrome-induced cell death. However, the inhibition of DT-diaphorase in U373MGsiGST6 cells, which have 74% of GSTM2 gene expression silenced, resulted in a more than 2-fold increase in cell death, suggesting that DT-diaphorase plays an important role in preventing aminochrome-induced toxicity in astrocytes.