| 16716839 |
Lee CS, Yim SB, Song JH, Han ES: Econazole attenuates cytotoxicity of 1-methyl-4-phenylpyridinium by suppressing mitochondrial membrane permeability transition. Brain Res Bull. 2006 May 31;69(6):687-94. Epub 2006 Apr 24.
Defects in mitochondrial function have been shown to participate in the induction of neuronal cell injury. The effect of econazole against the cytotoxicity of 1-methyl-4-phenylpyridinium (MPP (+)) in differentiated PC12 cells was assessed in relation to the mitochondrial membrane permeability changes. Treatment of PC12 cells with MPP (+) resulted in the nuclear damage, decrease in the mitochondrial transmembrane potential, cytosolic accumulation of cytochrome c, activation of caspase-3, increase in the formation of reactive oxygen species (ROS) and depletion of GSH. Econazole (0.25-2.5 microM) inhibited the cytotoxicity of MPP (+) or rotenone. The addition of econazole (0.5 microM) significantly attenuated the MPP (+)-induced mitochondrial damage, elevation of intracellular Ca (2+) level and cell death. However, because of the cytotoxicity, econazole at 5 microM did not attenuate the toxicity of MPP (+). The results show that econazole at the low concentrations may reduce the MPP (+)-induced viability loss in PC12 cells by suppressing the mitochondrial permeability transition, leading to activation of caspase-3 and the elevation of intracellular Ca (2+) levels, which are associated with the increased formation of ROS and depletion of GSH. |
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