7-Ketocholesterol enhances 1-methyl-4-phenylpyridinium-induced mitochondrial dysfunction and cell death in PC12 cells |
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Authors: | Y J Kim J H Han E S Han C S Lee |
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Institution: | (1) Department of Pharmacology, College of Medicine, Chung-Ang University, Seoul, South Korea |
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Abstract: | Summary. The present study investigated the promoting effect of oxysterol 7-ketocholesterol against the cytotoxicity of 1-methyl-4-phenylpyridinium
(MPP+) in differentiated PC12 cells. 7-Ketocholesterol significantly enhanced the MPP+-induced 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 and depletion of GSH. N-Acetylcysteine, ascorbate, trolox, carboxy-PTIO and Mn-TBAP reduced the cytotoxic effect of MPP+ in the presence of 7-ketocholesterol. The results indicate that 7-ketocholesterol shows a synergistic effect against the
cytotoxic effect of MPP+. 7-Ketocholesterol may enhance the MPP+-induced viability loss in PC12 cells by promoting the mitochondrial membrane permeability change, release of cytochrome c
and subsequent activation of caspase-3, which is associated with the increased formation of reactive oxygen species and depletion
of GSH. The findings suggest that 7-ketocholesterol as a promoting agent for the formation of mitochondrial permeability transition
may enhance the toxic neuronal cell injury. |
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Keywords: | : 1-Methyl-4-phenylpyridinium 7-ketocholesterol mitochondrial membrane permeability cell injury PC12 cells |
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