Differential Inhibition of MPP+- or 6-Hydroxydopamine-induced Cell Viability Loss in PC12 Cells by Trifluoperazine and W-7.
- Author:
Chung Soo LEE
1
Author Information
1. Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul 156-756, Korea. leecs@cau.ac.kr
- Publication Type:Original Article
- Keywords:
MPP+;
6-Hydroxydopamine;
Mitochondrial dysfunction;
Trifluoperazine;
W-7;
PC12 cells
- MeSH:
Animals;
Calmodulin;
Caspase 3;
Cell Death;
Cell Survival*;
Cytochromes c;
Cytosol;
Oxidopamine;
PC12 Cells*;
Permeability;
Reactive Oxygen Species;
Trifluoperazine*
- From:The Korean Journal of Physiology and Pharmacology
2005;9(4):247-253
- CountryRepublic of Korea
- Language:English
-
Abstract:
The present study assessed the effect of calmodulin antagonists trifluoperazine and W-7 against the cytotoxicity of MPP+ and 6-hydroxydopamine (6-OHDA) in relation to the mitochondrial dysfunction and cell death in PC12 cells. Trifluoperazine (an inhibitor of the mitochondrial permeability transition and calmodulin antagonist) and W-7 (a specific calmodulin antagonist) significantly attenuated the MPP+- induced cell viability loss in PC12 cells with a maximum inhibition at 0.5~1microM; beyond these concentrations the inhibitory effect declined. Both compounds at this concentration range did not cause cell death significantly. In contrast to MPP+, the trifluoperazine and W-7 did not depress the cytotoxic effect of 6-OHDA. Addition of trifluoperazine and W-7 inhibited the cytosolic accumulation of cytochrome c and caspase-3 activation in PC12 cells treated with MPP+ and attenuated the formation of reactive oxygen species and the depletion of GSH, whereas both compounds did not reduce the effect of 6-OHDA. The results show that trifluoperazine and W-7 may attenuate the cytotoxicity of MPP+ by inhibition of the mitochondrial permeability transition and calmodulin. Meanwhile, the cytotoxic effect of 6-OHDA seems to be mediated by the actions, which are different from MPP+.
