RGD Reference Report - Effects of anonaine on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. - Rat Genome Database

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

Authors: Lee, JJ  Jin, CM  Kim, YK  Ryu, SY  Lim, SC  Lee, MK 
Citation: Lee JJ, etal., Molecules. 2008 Feb 27;13(2):475-87.
RGD ID: 5129087
Pubmed: (View Article at PubMed) PMID:18305432

The effects of anonaine, an aporphine isoquinoline alkaloid, on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells were investigated. Anonaine at concentration ranges of 0.01-0.2 microM showed a significant inhibition of dopamine content at 24 h, with an IC(50) value of 0.05 microM. Anonaine at 0.05 microM inhibited tyrosine hydroxylase (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 was more influenced than AADC activity. Anonaine also decreased intracellular cyclic AMP levels, but not intracellular Ca(2+) concentrations. In addition, anonaine (0.05 microM) reduced L-DOPA (50 microM and 100 microM)-induced increases in dopamine content at 24 h. However, anonaine (0.05 microM) did not enhance L-DOPA (50 microM and 100 microM)-induced cell death after 24 h. These results suggest that anonaine inhibits dopamine biosynthesis by mainly reducing TH activity without aggravating L-DOPA-induced cytotoxicity in PC12 cells.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Ddc  (dopa decarboxylase)
Th  (tyrosine hydroxylase)


Additional Information