Effects of asimilobine on dopamine biosynthesis and l-DOPA-induced cytotoxicity in PC12 cells.
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.
Jin
Chun-Mei
CM
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, Cheongju, South Korea.
Lee
Jae-Joon
JJ
Kim
Young-Kyoon
YK
Ryu
Shi-Yong
SY
Lim
Sung-Cil
SC
Hwang
Bang-Yeon
BY
Lee
Chong-Kil
CK
Lee
Myung-Koo
MK
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001060:Aporphines / Q000737:chemistry / Q000494:pharmacology*; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D015259:Dopamine Agents / Q000737:chemistry / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D007980:Levodopa / Q000494:pharmacology*; D015394:Molecular Structure; D016716:PC12 Cells; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000970:Antineoplastic Agents; D001060:Aporphines; D015259:Dopamine Agents; D012333:RNA, Messenger; D007980:Levodopa; C054614:asimilobine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D004298:Dopamine