Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-1-27
pubmed:abstractText
C(2)-ceramide (C(2)-cer) and binding of the CD95/APO-1/FAS (aCD95) receptor are acknowledged inducers of apoptosis. In spite of that, their effects on the endoplasmic reticulum (ER) and mitochondria during early phases of apoptotic onset are poorly characterized. Here, by employing various approaches, we followed structural and functional modifications of these organelles at the beginning of cellular demise. In detail, we observed that C(2)-cer, but not CD95 activation, markedly modifies the morphology of the ER and promotes Ca(2+) release. Accordingly, mitochondria of C(2)-cer-treated, but not of CD95-stimulated, cells are fragmented, show reduced Ca(2+) uptake, and collapsed membrane potential (DeltaPsi(m)). Most notably, C(2)-cer-mediated morphological aberrations of the ER are prevented neither by the pan-caspase inhibitor Z-VADfmk nor by the cell cytoskeleton dissembler cytochalasin-D, while on the contrary they are reduced by incubation in the presence of the intracellular Ca(2+) chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA). We conclude that initiation of apoptosis via the intrinsic (i.e. C(2)-cer mediated) pathway causes an early structural and functional alteration of both ER and mitochondria, thus underlying a final "non return" point in the apoptotic pathway.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/1,2-bis(2-aminophenoxy)ethane-N,N,N'..., http://linkedlifedata.com/resource/pubmed/chemical/Amino Acid Chloromethyl Ketones, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Chelating Agents, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Proteinase Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid, http://linkedlifedata.com/resource/pubmed/chemical/N-acetylsphingosine, http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonylvalyl-alanyl-aspart...
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1090-2104
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
391
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
575-81
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Functional and structural alterations in the endoplasmic reticulum and mitochondria during apoptosis triggered by C2-ceramide and CD95/APO-1/FAS receptor stimulation.
pubmed:affiliation
Department of Experimental and Diagnostic Medicine, Section of General Pathology, Interdisciplinary Center for the Study of Inflammation and Emilia Romagna Laboratory BioPharmaNet, University of Ferrara, Ferrara, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't