The nuclear factor-kappaB (NF-κB) family plays an important role in the control of the apoptotic response. Its activation has been demonstrated in both neurons and glial cells in many neurological disorders. In the present study, we specifically examined whether and to what extent NF-κB activation is involved in culture models of Parkinson's disease following exposure of MN9D dopaminergic neuronal cells to 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenyl-4-phenylpyridinium ion (MPP +). Both analysis by immunocytochemistry and of immunoblots revealed that NF-κB-p65 was translocated into the nuclei following 6-OHDA but not MPP +-treatment. A time-dependent activation of NF-κB induced by 6-OHDA but not MPP + was also demonstrated by an electrophoretic mobility shift assay. A competition assay indicated that not only NF-κB-p65 but also -p50 is involved in 6-OHDA-induced NF-κB activity. Co-treatment with an antioxidant, N-acetyl-l-cysteine, blocked 6-OHDA-induced activation of NF-κB signaling. In the presence of an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), 6-OHDA-induced cell death was accelerated while PDTC did not affect MPP +-induced cell death. Our data may point to a drug-specific activation of NF-κB as a survival determinant for dopaminergic neurons.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2004 Sep 24|
Bibliographical noteFunding Information:
We thank Dr. George J. Markelonis of the University of Maryland at Baltimore for his critical reading of our manuscript. This work is supported by a grant by Brain Frontier 21 through BRC, and in part by the KOSEF through the Brain Disease Research Center at Ajou University and the Ministry of Health and Welfare (03-PJ1-PG10-21300-0023).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology