title: Effects of tributyltin acetate on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.
abstract: The effects of tributyltin acetate (TBTA) on dopamine biosynthesis and L-3,4-dihydroxyphenylalanine (L-DOPA)-induced cytotoxicity in PC12 cells were examined. TBTA at concentrations of 0.1-0.2 microM inhibited dopamine biosynthesis by reducing tyrosine hydroxylase (TH) activity and TH gene expression in PC12 cells. TBTA at 0.1-0.4 microM also reduced L-DOPA (20-50 microM)-induced increases in dopamine content for 24 h in PC12 cells. TBTA at concentrations up to 0.3 microM did not affect cell viability. However, TBTA at concentrations higher than 0.4 microM caused apoptotic cytotoxicity. Exposure of PC12 cells to non-cytotoxic (0.1 and 0.2 microM) or cytotoxic (0.4 microM) concentrations of TBTA with L-DOPA (20, 50 and 100 microM) significantly increased the cell loss and the percentage of apoptotic cells after 24 or 48 h compared with TBTA or L-DOPA alone. These data suggest that TBTA inhibits dopamine biosynthesis and enhances L-DOPA-induced cytotoxicity in PC12 cells.
authors: College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 12, Gaeshin-Dong, Heungduk-Gu, Cheongju 361-763, Korea.
authors: Yu Mi
authors: YM
authors: Kim
authors: Jae Joon
authors: JJ
authors: Lee
authors: Seung-Kook
authors: SK
authors: Park
authors: Sung Cil
authors: SC
authors: Lim
authors: Bang Yeon
authors: BY
authors: Hwang
authors: Chong Kil
authors: CK
authors: Lee
authors: Myung Koo
authors: MK
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects*; D004298:Dopamine / Q000096:biosynthesis*; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D007980:Levodopa / Q000494:pharmacology*; D016716:PC12 Cells; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
chemical_list: D014220:Trialkyltin Compounds; D007980:Levodopa; C011559:tributyltin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine