Catalponol enhances dopamine biosynthesis and protects against l-DOPA-induced cytotoxicity in PC12 cells

Abstract

The effects of catalponol (1) on dopamine biosynthesis and l-DOPA-induced cytotoxicity in PC12 cells were investigated. Catalponol at concentration ranges of 1–5 μM increased the intracellular levels of dopamine at 12–48 h. Catalponol at concentrations of up to 10 μM did not alter cell viability. Tyrosine hydroxylase (TH) activity was enhanced by 1 at 3 μM in a time-dependent manner, but aromatic l-amino acid decarboxylase activity was not. Catalponol also increased the intracellular levels of cyclic AMP and TH phosphorylation. In addition, catalponol at 3 μM associated with l-DOPA (20–50 μM) further enhanced the increases in dopamine levels induced by l-DOPA (50–100 μM) at 24 h. Catalponol at 2–5 μM inhibited l-DOPA (100–200 μM)-induced cytotoxicity at 48 h. These results suggest that 1 enhanced dopamine biosynthesis by inducing TH activity and protected against l-DOPA-induced cytotoxicity in PC12 cells, which was mediated by the increased levels of cyclic AMP.

Keywords:

• catalponol
• dopamine biosynthesis
• cyclic AMP
• tyrosine hydroxylase
• l-DOPA-induced cytotoxicity
• PC12 cells

Acknowledgements

This work was supported by a grant from the Technology Development Program for Agriculture and Forestry, Agricultural R&D Promotion Center/Ministry of Agriculture and Forestry, Republic of Korea (Contract/Grant No.: 204103-3, 2004-2007), and Research Center for Bioresource and Health, ITEP, and MKE.