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  Effects of asimilobine on dopamine biosynthesis and l-DOPA-induced cytotoxicity in PC12 cells
 
 
Titel: Effects of asimilobine on dopamine biosynthesis and l-DOPA-induced cytotoxicity in PC12 cells
Auteur: Jin, Chun-Mei
Lee, Jae-Joon
Kim, Young-Kyoon
Ryu, Shi-Yong
Lim, Sung-Cil
Hwang, Bang-Yeon
Lee, Chong-Kil
Lee, Myung-Koo
Verschenen in: Journal of Asian natural products research
Paginering: Jaargang 10 (2008) nr. 8 pagina's 737-745
Jaar: 2008-08
Inhoud: 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 μM showed a significant inhibition of intracellular dopamine levels for 24 h in a concentration-dependent manner with an IC50 value of 0.13 μM. Asimilobine at 0.15 μM 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 μM, but not 10 μM, did not alter cell viability toward PC12 cells. A non-cytotoxic asimilobine (0.15 μM) associated with l-DOPA (20, 50, and 100 μM) 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.
Uitgever: Taylor & Francis
Bronbestand: Elektronische Wetenschappelijke Tijdschriften
 
 

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