Inhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells
- Authors
- Lee, Chung Soo; Park, Se Young; Ko, Hyun Hee; Song, Jin Ho; Shin, Yong Kyoo; Han, Eun Sook
- Issue Date
- Jan-2005
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
- Keywords
- trifluoperazine; W-7; MPP+; mitochondrial membrane permeability; apoptotic cell death; PC12 cells
- Citation
- NEUROCHEMISTRY INTERNATIONAL, v.46, no.2, pp 169 - 178
- Pages
- 10
- Journal Title
- NEUROCHEMISTRY INTERNATIONAL
- Volume
- 46
- Number
- 2
- Start Page
- 169
- End Page
- 178
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/24681
- DOI
- 10.1016/j.neuint.2004.07.007
- ISSN
- 0197-0186
1872-9754
- Abstract
- Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of trifluoperazine and W-7 on the MPP+-induced mitochondrial damage and cell death in undifferentiated PC12 cells. Calmodulin antagonists (trifluoperazine, W-7 and calmidazolium) at 0.5-1 muM significantly reduced the loss of cell viability in PC12 cells treated with 500 muM MPP+. Trifluoperazine and W-7 (0.5-1 muM) inhibited the nuclear damage, the loss of the mitochondrial transmembrane potential followed by cytochrome c release, and the elevation of intracellular Ca2+ levels due to MPP+ in PC12 cells and attenuated the formation of reactive oxygen species and the depletion of GSH. Calmodulin antagonists at 5-10 muM exhibited a cytotoxic effect on PC12 cells, and compounds at 10 muM did not attenuate cytotoxicity of MPP+. Calmodulin antagonists (0.5-1 muM) significantly reduced rotenone-induced mitochondrial damage and cell death, whereas they did not attenuate cell death and elevation of intracellular Ca2+ levels due to H2O2 or ionomycin. The results show that trifluoperazine and W-7 exhibit a differential inhibitory effect against cytotoxicity of MPP+ depending on concentration. Both compounds at the concentrations less than 5 muM may attenuate the MPP+-induced viability loss in PC12 cells by suppressing change in the mitochondrial membrane permeability and by lowering the intracellular Ca2+ levels. (C) 2004 Elsevier Ltd. All rights reserved.
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