J Korean Neurol Assoc.  2010 Aug;28(3):157-165.

Role of Casein Kinase 2 in Parkinsonian Toxin 1-Methyl-4-phenylpyridinium-induced Cell Death

• Lee SY
• Hwang JY
• Han JH
• Kim DE
• Lee CS

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.

Keyword

4,5,6,7-Tetrabromobenzotriazole; 1-Methyl-4-phenylpyridinium; PC12 cells; Apoptosis-related proteins; Cell death

MeSH Terms

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
1-Methyl-4-phenylpyridinium
Casein Kinase II
Casein Kinases
Caseins
Caspase 3
Cytochromes c
Proteins
Triazoles