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J.Health Sci., 54(2), 244-249, 2008
Differential Role of Mitogen-Activated Protein Kinases in Response to Manganese Treatment in Substantia Nigra Dopaminergic Neurons
Seung Kim,a, # Euteum Park,a, b, #
Sung-Jun Kim,a and Hong Sung Chun*, a, b
aDepartment of Biotechnology (BK21 Program) and
bResearch Center for Proteineous Materials, Chosun University, 375 Seosuk-dong, Gwangju 501-759, Republic of Korea
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) mitogenactivated protein kinases were activated during DA cell death by MnCl2. Moreover, p 38 inhibition with SB203580, a specific inhibitor of p38, induced more toxic effects in MnCl2-treated cells. Among the p38 subfamily members, p38 α 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.
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