Fig. 10.

Mechanism of Mn effect on MEK5/ERK5 and apoptosis. The MN9D cells produce a large amount of ROS after manganese exposure; the oxidative stress activates the MEK/ERK5 cascade pathway. Phosphorylation of Bcl-2 by ERK5 reduces Bcl-2’s anti-apoptotic function, while the increased expression of Bax and Caspase-3 after Mn exposure enhances the pro-apoptotic activities. These effects, in combination, lead to a damaged mitochondrial membrane, increased ROS production, and aggravated apoptosis, and functionally reduces DA production and secretion.