Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2001-8-10
pubmed:abstractText
To elucidate the potential role of mitochondria in Taxol-induced cytotoxicity, we studied its direct mitochondrial effects. In Percoll-gradient purified liver mitochondria, Taxol induced large amplitude swelling in a concentration-dependent manner in the microM range. Opening of the permeability pore was also confirmed by the access of mitochondrial matrix enzymes for membrane impermeable substrates in Taxol-treated mitochondria. Taxol induced the dissipation of mitochondrial membrane potential (DeltaPsi) determined by Rhodamine123 release and induced the release of cytochrome c from the intermembrane space. All these effects were inhibited by 2.5 microM cyclosporine A. Taxol significantly increased the formation of reactive oxygen species (ROS) in both the aqueous and the lipid phase as determined by dihydrorhodamine123 and resorufin derivative. Cytochrome oxidase inhibitor CN(-), azide, and NO abrogated the Taxol-induced mitochondrial ROS formation while inhibitors of the other respiratory complexes and cyclosporine A had no effect. We confirmed that the Taxol-induced collapse of DeltaPsi and the induction of ROS production occurs in BRL-3A cells. In conclusion, Taxol-induced adenine nucleotide translocase-cyclophilin complex mediated permeability transition, and cytochrome oxidase mediated ROS production. Because both cytochrome c release and mitochondrial ROS production can induce suicide pathways, the direct mitochondrial effects of Taxol may contribute to its cytotoxicity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
548-58
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11498288-Animals, pubmed-meshheading:11498288-Antineoplastic Agents, Phytogenic, pubmed-meshheading:11498288-Apoptosis, pubmed-meshheading:11498288-Blotting, Western, pubmed-meshheading:11498288-Calcium, pubmed-meshheading:11498288-Carcinoma, Hepatocellular, pubmed-meshheading:11498288-Cyclosporine, pubmed-meshheading:11498288-Cytochrome c Group, pubmed-meshheading:11498288-Dose-Response Relationship, Drug, pubmed-meshheading:11498288-Formazans, pubmed-meshheading:11498288-Free Radicals, pubmed-meshheading:11498288-Humans, pubmed-meshheading:11498288-Kidney, pubmed-meshheading:11498288-Membrane Potentials, pubmed-meshheading:11498288-Microscopy, Confocal, pubmed-meshheading:11498288-Mitochondria, Heart, pubmed-meshheading:11498288-Mitochondria, Liver, pubmed-meshheading:11498288-Oxygen, pubmed-meshheading:11498288-Paclitaxel, pubmed-meshheading:11498288-Permeability, pubmed-meshheading:11498288-Rats, pubmed-meshheading:11498288-Rats, Wistar, pubmed-meshheading:11498288-Reactive Oxygen Species, pubmed-meshheading:11498288-Tetrazolium Salts, pubmed-meshheading:11498288-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Direct effect of Taxol on free radical formation and mitochondrial permeability transition.
pubmed:affiliation
Institute of Biochemistry, University of Pecs, Medical School, Pecs, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't