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Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju 361-763, Korea
College of Forest Science, Kookmin University, Seoul 136-702, Korea
Korea Research Institute of Chemical Technology, Taejeon 305-606, Korea
* Author to whom correspondence should be addressed.
Received: 30 January 2008; in revised form: 22 February 2008 / Accepted: 25 February 2008 / Published: 27 February 2008
(This article belongs to the Special Issue Alkaloids
Abstract: The effects of anonaine, an aporphine isoquinoline alkaloid, on dopaminebiosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaineat concentration ranges of 0.01-0.2 μM showed a significant inhibition of dopaminecontent at 24 h, with an IC50 value of 0.05 μM. Anonaine at 0.05 μM inhibited tyrosinehydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities to 38.4-40.2% and 78.4-90.2% of control levels at 12-24 h and 3-6 h, respectively. TH activity wasmore influenced than AADC activity. Anonaine also decreased intracellular cyclic AMPlevels, but not intracellular Ca2+ concentrations. In addition, anonaine (0.05 μM) reducedL-DOPA (50 μM and 100 μM)-induced increases in dopamine content at 24 h. However,anonaine (0.05 μM) did not enhance L-DOPA (50 μM and 100 μM)-induced cell death 476after 24 h. These results suggest that anonaine inhibits dopamine biosynthesis by mainlyreducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells.
Keywords: Anonaine; Dopamine biosynthesis; L-DOPA-induced cytotoxicity; PC12 cells.
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Lee, J.J.; Jin, C.M.; Kim, Y.K.; Ryu, S.Y.; Lim, S.C.; Lee, M.K. Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells. Molecules 2008, 13, 475-487.
Lee JJ, Jin CM, Kim YK, Ryu SY, Lim SC, Lee MK. Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells. Molecules. 2008; 13(2):475-487.
Lee, Jae J.; Jin, Chun M.; Kim, Young K.; Ryu, Shi Y.; Lim, Sung C.; Lee, Myung K. 2008. "Effects of Anonaine on Dopamine Biosynthesis and L-DOPA-Induced Cytotoxicity in PC12 Cells." Molecules 13, no. 2: 475-487.