Neurorescue by a ROS Decomposition Catalyst.

Abstract

The effect of the bis-sulfonated iron(III) corrole (1-Fe), a potent decomposition catalyst of reactive oxygen species, on rescuing SN4741 cells that were damaged by 6-hydroxydopamine (6-OHDA) was investigated as an in vitro model system for studying cell death of dopaminergic neurons in the substantia nigra. Important findings that accompanied the ability to rescue dopaminergic neurons were increased expression of phenotypic dopaminergic proteins, such as tyrosine hydroxylase (TH) and dopamine transporter (DAT), which were significantly depleted upon 6-OHDA-mediated damage. 1-Fe also elevated expression levels of aldehyde dehydrogenase 1 (ALDH-1), previously disclosed as a cardinal protein in the pathogenesis of Parkinson's disease. Since these findings suggested that 1-Fe affects quite a wide range of intracellular mechanisms, vital intracellular pathways that involve neuroplasticity, growth, differentiation and survival of neurons, were examined. Phosphatidylinositol 3-kinase (PI3K) and protein kinase c (PKC) were found to be involved, as pharmacological inhibitors of these kinases abolished the neurorescue effect of 1-Fe. 1-Fe also elevated the expression of antiapoptotic protein Bcl-2, which is essential for proper mitochondrial function and cellular survival. The overall conclusion is that 1-Fe is capable of rescuing already damaged neuronal cells by a variety of mechanisms that are beyond its antioxidant activity.