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Effects of asimilobine on dopamine biosynthesis and l-DOPA-induced cytotoxicity in PC12 cells.

Authors: Jin, CM  Lee, JJ  Kim, YK  Ryu, SY  Lim, SC  Hwang, BY  Lee, CK  Lee, MK 
Citation: Jin CM, etal., J Asian Nat Prod Res. 2008 Jul-Aug;10(7-8):747-55.
Pubmed: (View Article at PubMed) PMID:18696327
DOI: Full-text: DOI:10.1080/10286020802030892

The effects of asimilobine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Asimilobine at concentration ranges of 0.05-0.2 microM showed a significant inhibition of intracellular dopamine levels for 24 h in a concentration-dependent manner with an IC50 value of 0.13 microM. Asimilobine at 0.15 microM inhibited tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) activities at 24 h (73.2% inhibition of TH activity): the inhibition of TH activity was stronger and longer than that of AADC activity. Asimilobine also decreased TH mRNA levels and intracellular cyclic AMP levels, but not the basal Ca2+ concentrations. In addition, asimilobine at 0.05-5.0 microM, but not 10 microM, did not alter cell viability toward PC12 cells. A non-cytotoxic asimilobine (0.15 microM) associated with l-DOPA (20, 50, and 100 microM) for 24 h inhibited L-DOPA-induced increases in dopamine levels and enhanced L-DOPA-induced cell death when compared with L-DOPA alone. These results suggest that asimilobine inhibits dopamine biosynthesis by mainly reducing the TH activity and TH mRNA expression, and enhances L-DOPA-induced cytotoxicity in PC12 cells.

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CRRD Object Information
CRRD ID: 5129084
Created: 2011-03-23
Species: All species
Last Modified: 2011-03-23
Status: ACTIVE



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