Abstract
The release of holocytochrome c (cyt c) from mitochondria into the cytosol is reportedly a landmark of the execution phase of apoptosis. As shown here, the P-glycoprotein- (P-gp) expressing K562/ADR cell line (but not the parental K562 cell line) exhibits both cytosolic and mitochondrial cyt c in the absence of any signs of apoptosis. K562/ADR cells were found to be relatively resistant to a variety of different inducers of apoptosis, and blocking the P-gp did not reverse this resistance. The release of cyt c in non-apoptotic K562/ADR cells was not accompanied by that of any other mitochondrial apoptogenic protein, such as AIF or Smac/DIABLO, and was inhibited by Bcl-2 over expression. In addition, using a cell-free system, we show that mitochondria isolated from K562/ADR cells spontaneously released cyt c. These data suggest that cyt c release may be compatible with the preservation of mitochondrial integrity and function, as well as cell proliferation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Apoptosis
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Apoptosis Regulatory Proteins
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Blotting, Western
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Cell Line
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Cell Line, Tumor
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Cell Proliferation
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Cytochromes c / metabolism*
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Cytosol / metabolism*
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Dose-Response Relationship, Drug
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Drug Resistance, Neoplasm*
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Electrophoresis, Polyacrylamide Gel
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Enzyme Activation
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Enzyme-Linked Immunosorbent Assay
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Gene Expression Regulation, Neoplastic*
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Humans
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Intracellular Signaling Peptides and Proteins / metabolism
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K562 Cells
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Leukemia / metabolism*
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Microscopy, Confocal
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Microscopy, Electron
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Mitochondria / metabolism
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Mitochondrial Proteins / metabolism
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Polymerase Chain Reaction
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Time Factors
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Transfection
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Apoptosis Regulatory Proteins
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DIABLO protein, human
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Intracellular Signaling Peptides and Proteins
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Mitochondrial Proteins
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Proto-Oncogene Proteins c-bcl-2
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Cytochromes c