Figure 2

Pathway of peroxynitrite-induced toxicity to mature oligodendrocytes. Peroxynitrite triggers zinc release from metallothionein and/or mitochondria either directly or indirectly via the conversion of reduced glutathione (GSH) to oxidized glutathione (GSSG). Zinc induces ERK1/2 phosphorylation, which may be due partially to the inhibition of MKP activity. In contrast to neurons, ERK1/2 phosphorylation occurs upstream of 12-LOX in mature oligodendrocytes. ROS generated from 12-LOX activation and mitochondria are toxic to mature oligodendrocytes.