Catalponol enhances dopamine biosynthesis and protects against L-DOPA-induced cytotoxicity in PC12 cells.
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 microM increased the intracellular levels of dopamine at 12-48 h. Catalponol at concentrations of up to 10 microM did not alter cell viability. Tyrosine hydroxylase (TH) activity was enhanced by 1 at 3 microM 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 microM associated with L-DOPA (20-50 microM) further enhanced the increases in dopamine levels induced by L-DOPA (50-100 microM) at 24 h. Catalponol at 2-5 microM inhibited L-DOPA (100-200 microM)-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.
Huang
Hai-Shan
HS
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju 361-763, South Korea.
Han
Xiang-Hua
XH
Hwang
Bang-Yeon
BY
Park
Jae-In
JI
Yoo
Se-Kuel
SK
Choi
Hyun-Sook
HS
Lim
Sung-Cil
SC
Lee
Myung-Koo
MK
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004298:Dopamine / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007980:Levodopa / Q000494:pharmacology*; D009284:Naphthols / Q000008:administration & dosage / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
D009284:Naphthols; C013432:catalponol; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine