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Econazole attenuates cytotoxicity of 1-methyl-4-phenylpyridinium by suppressing mitochondrial membrane permeability transition.
Brain Res Bull. 2006 May 31; 69(6):687-94.BR

Abstract

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.

Authors+Show Affiliations

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

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16716839

Citation

Lee, Chung Soo, et al. "Econazole Attenuates Cytotoxicity of 1-methyl-4-phenylpyridinium By Suppressing Mitochondrial Membrane Permeability Transition." Brain Research Bulletin, vol. 69, no. 6, 2006, pp. 687-94.
Lee CS, Yim SB, Song JH, et al. Econazole attenuates cytotoxicity of 1-methyl-4-phenylpyridinium by suppressing mitochondrial membrane permeability transition. Brain Res Bull. 2006;69(6):687-94.
Lee, C. S., Yim, S. B., Song, J. H., & Han, E. S. (2006). Econazole attenuates cytotoxicity of 1-methyl-4-phenylpyridinium by suppressing mitochondrial membrane permeability transition. Brain Research Bulletin, 69(6), 687-94.
Lee CS, et al. Econazole Attenuates Cytotoxicity of 1-methyl-4-phenylpyridinium By Suppressing Mitochondrial Membrane Permeability Transition. Brain Res Bull. 2006 May 31;69(6):687-94. PubMed PMID: 16716839.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Econazole attenuates cytotoxicity of 1-methyl-4-phenylpyridinium by suppressing mitochondrial membrane permeability transition. AU - Lee,Chung Soo, AU - Yim,Soo Bin, AU - Song,Jin Ho, AU - Han,Eun Sook, Y1 - 2006/04/24/ PY - 2006/01/31/received PY - 2006/03/19/revised PY - 2006/03/28/accepted PY - 2006/5/24/pubmed PY - 2006/8/5/medline PY - 2006/5/24/entrez SP - 687 EP - 94 JF - Brain research bulletin JO - Brain Res Bull VL - 69 IS - 6 N2 - 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. SN - 0361-9230 UR - https://www.unboundmedicine.com/medline/citation/16716839/Econazole_attenuates_cytotoxicity_of_1_methyl_4_phenylpyridinium_by_suppressing_mitochondrial_membrane_permeability_transition_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(06)00118-3 DB - PRIME DP - Unbound Medicine ER -