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rdf:type |
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lifeskim:mentions |
umls-concept:C0010749,
umls-concept:C0021469,
umls-concept:C0030685,
umls-concept:C0032433,
umls-concept:C0162638,
umls-concept:C0333668,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1292733,
umls-concept:C1963578
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pubmed:issue |
6
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pubmed:dateCreated |
2002-5-8
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pubmed:abstractText |
We have shown previously that depletion of polyamines delays apoptosis induced by camptothecin in rat intestinal epithelial cells (IEC-6). Mitochondria play an important role in the regulation of apoptosis in mammalian cells because apoptotic signals induce mitochondria to release cytochrome c. The latter interacts with Apaf-1 to activate caspase-9, which in turn activates downstream caspase-3. Bcl-2 family proteins are involved in the regulation of cytochrome c release from mitochondria. In this study, we examined the effects of polyamine depletion on the activation of the caspase cascade, release of cytochrome c from mitochondria, and expression and translocation of Bcl-2 family proteins. We inhibited ornithine decarboxylase, the first rate-limiting enzyme in polyamine synthesis, with alpha-difluoromethylornithine (DFMO) to deplete cells of polyamines. Depletion of polyamines prevented camptothecin-induced release of cytochrome c from mitochondria and decreased the activity of caspase-9 and caspase-3. The mitochondrial membrane potential was not disrupted when cytochrome c was released. Depletion of polyamines decreased translocation of Bax to mitochondria during apoptosis. The expression of antiapoptotic proteins Bcl-x(L) and Bcl-2 was increased in DFMO-treated cells. Caspase-8 activity and cleavage of Bid were decreased in cells depleted of polyamines. These results suggest that polyamine depletion prevents IEC-6 cells from apoptosis by preventing the translocation of Bax to mitochondria, thus preventing the release of cytochrome c.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death...,
http://linkedlifedata.com/resource/pubmed/chemical/Bax protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Bid protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Camptothecin,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp8 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Casp9 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 9,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group,
http://linkedlifedata.com/resource/pubmed/chemical/Eflornithine,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ornithine Decarboxylase,
http://linkedlifedata.com/resource/pubmed/chemical/Polyamines,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0363-6143
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
282
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C1290-7
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11997243-Animals,
pubmed-meshheading:11997243-Apoptosis,
pubmed-meshheading:11997243-BH3 Interacting Domain Death Agonist Protein,
pubmed-meshheading:11997243-Blotting, Western,
pubmed-meshheading:11997243-Camptothecin,
pubmed-meshheading:11997243-Carrier Proteins,
pubmed-meshheading:11997243-Caspase 3,
pubmed-meshheading:11997243-Caspase 8,
pubmed-meshheading:11997243-Caspase 9,
pubmed-meshheading:11997243-Caspases,
pubmed-meshheading:11997243-Cell Line,
pubmed-meshheading:11997243-Cytochrome c Group,
pubmed-meshheading:11997243-DNA Fragmentation,
pubmed-meshheading:11997243-Eflornithine,
pubmed-meshheading:11997243-Enzyme Inhibitors,
pubmed-meshheading:11997243-Epithelial Cells,
pubmed-meshheading:11997243-Intestinal Mucosa,
pubmed-meshheading:11997243-Mitochondria,
pubmed-meshheading:11997243-Ornithine Decarboxylase,
pubmed-meshheading:11997243-Polyamines,
pubmed-meshheading:11997243-Proto-Oncogene Proteins,
pubmed-meshheading:11997243-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11997243-Rats,
pubmed-meshheading:11997243-bcl-2-Associated X Protein
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pubmed:year |
2002
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pubmed:articleTitle |
Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the release of cytochrome c.
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pubmed:affiliation |
Department of Physiology, The University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
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pubmed:publicationType |
Journal Article
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