Role of Casein Kinase 2 in Parkinsonian Toxin 1-Methyl-4-phenylpyridinium-induced Cell Death.
- Author:
Seung Yeon LEE
1
;
Jung Yun HWANG
;
Jeong Ho HAN
;
Doo Eung KIM
;
Chung Soo LEE
Author Information
1. Department of Neurology, Seoul Veterans Hospital, Seoul, Korea.
- Publication Type:Original Article
- Keywords:
4,5,6,7-Tetrabromobenzotriazole;
1-Methyl-4-phenylpyridinium;
PC12 cells;
Apoptosis-related proteins;
Cell death
- MeSH:
1-Methyl-4-phenylpyridinium;
Animals;
Apoptosis;
Casein Kinase II;
Casein Kinases;
Caseins;
Caspase 3;
Cell Death;
Cytochromes c;
Neurons;
PC12 Cells;
Proteins;
Signal Transduction;
Triazoles
- From:Journal of the Korean Neurological Association
2010;28(3):157-165
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Protein casein kinase 2 is involved in signal transduction, cell growth, and apoptosis. However, it has not been elucidated whether parkinsonian toxin 1-methyl-4-phenylpyridinium (MPP+)-induced neuronal cell death is mediated by a casein-kinase-2-mediated pathway. METHODS: We monitored apoptosis-related protein activation, changes in the level of casein kinase 2, nuclear damage, and apoptosis in differentiated PC12 cells exposed to MPP+ in combination with casein kinase 2 inhibitor. RESULTS: Casein kinase 2 inhibitors [4,5,6,7-tetrabromobenzotriazole (TBB), 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole, and apigenin] reduced MPP+- and rotenone-induced cell death in differentiated PC12 cells. TBB inhibited the MPP+-induced activation of apoptosis-related proteins (decreases in Bid and Bcl-2 levels, increase in Bax levels, cytochrome c release, and caspase-3 activation), increase in casein kinase 2 levels, and nuclear damage. CONCLUSIONS: Administering casein kinase 2 inhibitor TBB at concentrations that do not induce toxic effects may reduce MPP+-induced cell death in differentiated PC12 cells by suppressing the apoptosis-related protein activation that leads to cytochrome c release and subsequent activation of caspase-3. The results suggest that MPP+-induced cell death process is mediated by a casein kinase 2 pathway.
