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http://dx.doi.org/10.1080/19768354.2011.611256

Perphenazine and trifluoperazine induce mitochondria-mediated cell death in SH-SY5Y cells  

Hong, Seok-Heon (Sejong University, Molecular Biology)
Lee, Min-Yeong (Sejong University, Molecular Biology)
Shin, Ki-Soon (Kyung Hee University)
Kang, Shin-Jung (Sejong University, Molecular Biology)
Publication Information
Animal cells and systems / v.16, no.1, 2012 , pp. 20-26 More about this Journal
Abstract
Drug-induced parkinsonism has been associated with an increased risk for Parkinson's disease. Antipsychotic drugs have long been known to cause parkinsonian symptoms. However, it remains unclear whether antipsychotics can directly damage the nigrostriatal pathway. In the present study, we investigated the toxicity mechanism of two typical antipsychotics, perphenazine and trifluoperazine, in a human dopaminergic cell line, SH-SY5Y. Perphenazine and trifluoperazine induced mitochondrial damage as evidenced by fragmentation of mitochondria, activation of Bax, cytochrome c release and a decrease in cellular ATP level. In addition, activation of caspase-3 and apoptotic nuclei were observed following the drug treatment. However, pan-caspase inhibitor did not suppress the cell death induced by the antipsychotics, suggesting that the initiated apoptosis was possibly shifted to necrosis upon caspase inhibition. Damaged mitochondria may have induced oxidative stress since the drug-induced cell death was partially suppressed by an antioxidant. Taken together, our results suggest that perphenazine and trifluoperazine can induce apoptotic cell death in a dopaminergic cell line via mitochondrial damage accompanied by oxidative stress.
Keywords
perphenazine; trifluoperazine; antipsychotics; parkinsonism; mitochondria;
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