Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2003-8-11
pubmed:abstractText
Activated human T lymphocytes exposed to apoptotic stimuli targeting mitochondria (i.e. staurosporine), enter an early, caspase-independent phase of commitment to apoptosis characterized by cell shrinkage and peripheral chromatin condensation. We show that during this phase, AIF is selectively released from the intermembrane space of mitochondria, and that Bax undergo conformational change, relocation to mitochondria, and insertion into the outer mitochondrial membrane, in a Bid-independent manner. We analyzed the subcellular distribution of cathepsins (Cat) B, D, and L, in a search for caspase-independent factors responsible for Bax activation and AIF release. All were translocated from lysosomes to the cytosol, in correlation with limited destabilization of the lysosomes and release of lysosomal molecules in a size selective manner. However, only inhibition of Cat D activity by pepstatin A inhibited the early apoptotic events and delayed cell death, even in the presence of bafilomycin A1, an inhibitor of vacuolar type H+-ATPase, which inhibits acidification in lysosomes. Small interfering RNA-mediated gene silencing was used to inactivate Cat D, Bax, and AIF gene expression. This allowed us to define a novel sequence of events in which Cat D triggers Bax activation, Bax induces the selective release of mitochondrial AIF, and the latter is responsible for the early apoptotic phenotype.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AIFM1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents, http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Inducing Factor, http://linkedlifedata.com/resource/pubmed/chemical/BAX protein, human, http://linkedlifedata.com/resource/pubmed/chemical/BH3 Interacting Domain Death..., http://linkedlifedata.com/resource/pubmed/chemical/BID protein, human, http://linkedlifedata.com/resource/pubmed/chemical/CTSL1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin B, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin D, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin L, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Flavoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Macrolides, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Pepstatins, http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors, 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/RNA, Small Interfering, http://linkedlifedata.com/resource/pubmed/chemical/Staurosporine, http://linkedlifedata.com/resource/pubmed/chemical/bafilomycin A1, http://linkedlifedata.com/resource/pubmed/chemical/bcl-2-Associated X Protein, http://linkedlifedata.com/resource/pubmed/chemical/pepstatin
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
31401-11
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:12782632-Anti-Bacterial Agents, pubmed-meshheading:12782632-Apoptosis, pubmed-meshheading:12782632-Apoptosis Inducing Factor, pubmed-meshheading:12782632-BH3 Interacting Domain Death Agonist Protein, pubmed-meshheading:12782632-Carrier Proteins, pubmed-meshheading:12782632-Cathepsin B, pubmed-meshheading:12782632-Cathepsin D, pubmed-meshheading:12782632-Cathepsin L, pubmed-meshheading:12782632-Cathepsins, pubmed-meshheading:12782632-Cells, Cultured, pubmed-meshheading:12782632-Cysteine Endopeptidases, pubmed-meshheading:12782632-Cytosol, pubmed-meshheading:12782632-Down-Regulation, pubmed-meshheading:12782632-Enzyme Inhibitors, pubmed-meshheading:12782632-Flavoproteins, pubmed-meshheading:12782632-Humans, pubmed-meshheading:12782632-Hydrogen-Ion Concentration, pubmed-meshheading:12782632-Lysosomes, pubmed-meshheading:12782632-Macrolides, pubmed-meshheading:12782632-Membrane Proteins, pubmed-meshheading:12782632-Mitochondria, pubmed-meshheading:12782632-Pepstatins, pubmed-meshheading:12782632-Phenotype, pubmed-meshheading:12782632-Protease Inhibitors, pubmed-meshheading:12782632-Proto-Oncogene Proteins, pubmed-meshheading:12782632-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12782632-RNA, Small Interfering, pubmed-meshheading:12782632-Signal Transduction, pubmed-meshheading:12782632-Staurosporine, pubmed-meshheading:12782632-T-Lymphocytes, pubmed-meshheading:12782632-bcl-2-Associated X Protein
pubmed:year
2003
pubmed:articleTitle
Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis.
pubmed:affiliation
Laboratoire de Greffes d'Epithéliums et Régulation de l'Activation Lymphocytaire, Unité INSERM 542, Hôpital Paul Brousse, Villejuif, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't