Effects of tributyltin acetate on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells.
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.
Kim
Yu Mi
YM
College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 12, Gaeshin-Dong, Heungduk-Gu, Cheongju 361-763, Korea.
Lee
Jae Joon
JJ
Park
Seung-Kook
SK
Lim
Sung Cil
SC
Hwang
Bang Yeon
BY
Lee
Chong Kil
CK
Lee
Myung Koo
MK
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
D014220:Trialkyltin Compounds; D007980:Levodopa; C011559:tributyltin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine