Differential Role of Mitogen-Activated Protein Kinases in Response to Manganese Treatment in Substantia Nigra Dopaminergic Neurons

Abstract

Recent studies have provided evidence that exposure to manganese (Mn) induces Parkinson's disease (PD)-like symptoms. We investigated the mechanism of Mn neurotoxicity in the SN4741 dopaminergic (DA) neuronal cell line. The results indicated that the p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases were activated during DA cell death by MnCl₂. Moreover, p38 inhibition with SB203580, a specific inhibitor of p38, induced more toxic effects in MnCl₂-treated cells. Among the p38 subfamily members, p38α attenuated the caspase-3 activation and cell death induced by MnCl₂. However, the expression of JNK stimulated the activity of caspase-3 and mediated the Mn-induced cell death. These results suggest that there are multiple pathways in MnCl₂-induced DA neuronal cell death.