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J Korean Neurol Assoc. 2010;28(3):157-165.
- Role of Casein Kinase 2 in Parkinsonian Toxin
1-Methyl-4-phenylpyridinium-induced Cell Death
-
Seung-Yeon Lee
-
Department of Neurology, Seoul Veterans Hospital, Department of Pharmacology
a
, Chung-Ang University
College of Medicine, Seoul, Korea
- 파킨슨증후군 유발독소 1-methyl-4-phenylpyridinium에
의한 세포사멸에 있어 카세인키나아제 2 (casein
kinase 2)의 역할
-
이승연, 황정연 한정호 김두응 이정수
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서울보훈병원 신경과, 중앙대학교 의과대학 약리학교실
- 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-β-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. Key Words: 4,5,6,7-Tetrabromobenzotriazole, 1-Methyl-4-phenylpyridinium, PC12 cells, Apoptosis-related proteins,
Cell death
Keywords :
- 초록
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