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Effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells

Title
Effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells
Authors
Yang Y.J.Lee H.J.Huang H.S.Lee B.K.Choi H.S.Lim S.C.Lee C.K.Lee M.K.
Ewha Authors
이병구
SCOPUS Author ID
이병구scopusscopus
Issue Date
2009
Journal Title
Journal of Neuroscience Research
ISSN
0360-4012JCR Link
Citation
vol. 87, no. 8, pp. 1929 - 1937
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
The effects of scoparone on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. PC12 cells treated with scoparone at concentrations of 100-200 μM showed a 128-136% increase in dopamine levels over the course of 24 hr. Scoparone significantly increased the secretion of dopamine into the culture medium. Under the same conditions, the activities of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) were enhanced by treatment with 200 lM scoparone for 6-48 hr, but the activity of TH was regulated for a longer period than that of AADC. The intracellular levels of cyclic AMP and Ca 2+ were increased by treatment with 200 μM scoparone. The levels of TH mRNA and the phosphorylation of cyclic AMP-response elementbinding protein (CREB) were also significantly increased by treatment with 200 μM scoparone. In addition, scoparone at a concentration of 200 μM stimulated the activities of cyclic AMP-dependent protein kinase (PKA), protein kinase C (PKC), and Ca 2+/calmodulin kinase II (CaMK II). Finally, pretreatment with 200 μM scoparone reduced the cytotoxicity induced by L-DOPA (20-100 μM) at 24 hr. These results suggest that scoparone enhances dopamine biosynthesis by regulating TH activity and TH gene expression, which is mediated by the PKA, CREB, PKC, and CaMK II pathways, and protects cells from L-DOPA-induced cytotoxicity by inducing cyclic AMP-PKA systems in PC12 cells. © 2009 Wiley-Liss, Inc.
DOI
10.1002/jnr.22009
Appears in Collections:
약학대학 > 약학과 > Journal papers
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