Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0010749,
umls-concept:C0018284,
umls-concept:C0037083,
umls-concept:C0127400,
umls-concept:C0162638,
umls-concept:C0205263,
umls-concept:C0205266,
umls-concept:C0205282,
umls-concept:C0301625,
umls-concept:C0376515,
umls-concept:C0392747,
umls-concept:C1547671,
umls-concept:C1707312,
umls-concept:C1710082,
umls-concept:C2323499
|
| pubmed:issue |
4
|
| pubmed:dateCreated |
1998-9-10
|
| pubmed:abstractText |
It has been shown that cytochrome c is released from mitochondria during apoptosis, activates pro-caspase CPP32 (caspase III), and induces DNA fragmentation in mixtures of cytosolic extracts and isolated nuclei. To establish whether cytochrome c can primarily induce apoptosis in intact cells, we used direct electroporation of cytochrome c into murine interleukin-3 (IL-3)-dependent cells. Electroporation of micromolar external concentrations of cytochrome c rapidly induced apoptosis (2 to 4 hours) that was concentration-dependent, did not affect mitochondrial transmembrane potential, and was independent of cell growth. Only certain isoforms of cytochrome c were apoptogenic; yeast cytochrome c and other redox proteins were inactive. Cytochrome c-induced apoptosis was dependent on heme attachment to the apo-enzyme and was completely abolished by caspase inhibitors. Nonapoptogenic isoforms of cytochrome c did not compete for apoptogenic cytochrome c. Although apoptosis induced by IL-3 withdrawal was inhibited by bcl-2 overexpression and expression of an activated MAP-kinase-kinase (MAP-KK), cytochrome c induced apoptosis in the presence of IL-3 signaling, bcl-2 over-expression, expression of activated MAP-KK, and the combined antiapoptotic action of all three. Cytochrome c also induced apoptosis in the leukemic cell line WEHI 3b. However, human HL60 and CEM cells were resistant to cytochrome c-induced apoptosis. HL60 cells did not electroporate, but CEM cells were efficiently electroporated. Our studies with IL-3-dependent cells confirm that the apoptogenic attributes of cytochrome c are identical in intact cells to those in cell extracts. We conclude that cytochrome c can be a prime initiator of apoptosis in intact growing cells and acts downstream of bcl-2 and mitochondria, but that other cells are resistant to its apoptogenic activity. The system described offers a novel, simple approach for investigating regulation of apoptosis by cytochrome c and provides a model linking growth factor signaling to metabolism, survival, and apoptosis control.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Hematopoietic Cell Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-3,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
|
| pubmed:issn |
0006-4971
|
| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 1998 by The American Society of Hematology.
|
| pubmed:issnType |
Print
|
| pubmed:day |
15
|
| pubmed:volume |
92
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
1235-46
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9694712-Animals,
pubmed-meshheading:9694712-Apoptosis,
pubmed-meshheading:9694712-Caspase 3,
pubmed-meshheading:9694712-Caspases,
pubmed-meshheading:9694712-Cattle,
pubmed-meshheading:9694712-Cell Line,
pubmed-meshheading:9694712-Cell Transformation, Neoplastic,
pubmed-meshheading:9694712-Cysteine Endopeptidases,
pubmed-meshheading:9694712-Cytochrome c Group,
pubmed-meshheading:9694712-Enzyme Induction,
pubmed-meshheading:9694712-Hematopoietic Cell Growth Factors,
pubmed-meshheading:9694712-Hematopoietic Stem Cells,
pubmed-meshheading:9694712-Humans,
pubmed-meshheading:9694712-Interleukin-3,
pubmed-meshheading:9694712-Leukemia, Experimental,
pubmed-meshheading:9694712-Mice,
pubmed-meshheading:9694712-Mitochondria,
pubmed-meshheading:9694712-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:9694712-Models, Biological,
pubmed-meshheading:9694712-Protein Kinase Inhibitors,
pubmed-meshheading:9694712-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:9694712-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:9694712-Signal Transduction,
pubmed-meshheading:9694712-Tumor Cells, Cultured
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Cytochrome c induces caspase-dependent apoptosis in intact hematopoietic cells and overrides apoptosis suppression mediated by bcl-2, growth factor signaling, MAP-kinase-kinase, and malignant change.
|
| pubmed:affiliation |
Institute for Clinical Science, Exeter University, Noy Scott House, Wonford, Exeter, UK.
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
|