Effects of tri butyl tin acetate on dopamine biosynthesis and l-dopa-lnduced cytotoxicity in pc12 cells |
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Authors: | Yu Mi Kim Jae Joon Lee Seung -Kook Park Sung Cil Lim Bang Yeon Hwang Chong Kil Lee Myung Koo Lee |
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Institution: | College of Pharmacy and Research Center for Bioresource and Health, Chungbuk National University, 12, Gaeshin-Dong, Heungduk-Gu, Cheongju 361-763, Korea. |
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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. |
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Keywords: | Tributyltin acetate Dopamine content Tyrosine hydroxylase L-DOPA Cytotoxicity Apoptosis PC 12 cells |
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