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Inhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells.
Neurochem Int. 2005 Jan; 46(2):169-78.NI

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 microM significantly reduced the loss of cell viability in PC12 cells treated with 500 microM MPP+. Trifluoperazine and W-7 (0.5-1 microM) 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 microM exhibited a cytotoxic effect on PC12 cells, and compounds at 10 microM did not attenuate cytotoxicity of MPP+. Calmodulin antagonists (0.5-1 microM) 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 microM 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.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, South Korea. leecs@cau.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15627517

Citation

Lee, Chung Soo, et al. "Inhibition of MPP+-induced Mitochondrial Damage and Cell Death By Trifluoperazine and W-7 in PC12 Cells." Neurochemistry International, vol. 46, no. 2, 2005, pp. 169-78.
Lee CS, Park SY, Ko HH, et al. Inhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells. Neurochem Int. 2005;46(2):169-78.
Lee, C. S., Park, S. Y., Ko, H. H., Song, J. H., Shin, Y. K., & Han, E. S. (2005). Inhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells. Neurochemistry International, 46(2), 169-78.
Lee CS, et al. Inhibition of MPP+-induced Mitochondrial Damage and Cell Death By Trifluoperazine and W-7 in PC12 Cells. Neurochem Int. 2005;46(2):169-78. PubMed PMID: 15627517.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of MPP+-induced mitochondrial damage and cell death by trifluoperazine and W-7 in PC12 cells. AU - Lee,Chung Soo, AU - Park,Se Young, AU - Ko,Hyun Hee, AU - Song,Jin Ho, AU - Shin,Yong Kyoo, AU - Han,Eun Sook, PY - 2004/05/12/received PY - 2004/07/08/revised PY - 2004/07/28/accepted PY - 2005/1/4/pubmed PY - 2005/3/10/medline PY - 2005/1/4/entrez SP - 169 EP - 78 JF - Neurochemistry international JO - Neurochem Int VL - 46 IS - 2 N2 - 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 microM significantly reduced the loss of cell viability in PC12 cells treated with 500 microM MPP+. Trifluoperazine and W-7 (0.5-1 microM) 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 microM exhibited a cytotoxic effect on PC12 cells, and compounds at 10 microM did not attenuate cytotoxicity of MPP+. Calmodulin antagonists (0.5-1 microM) 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 microM 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. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/15627517/Inhibition_of_MPP+_induced_mitochondrial_damage_and_cell_death_by_trifluoperazine_and_W_7_in_PC12_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(04)00157-3 DB - PRIME DP - Unbound Medicine ER -