File Download
There are no files associated with this item.
Links for fulltext
(May Require Subscription)
- Publisher Website: 10.1084/jem.192.4.571
- Scopus: eid_2-s2.0-0034698733
- PMID: 10952727
- WOS: WOS:000089067600013
- Find via
Supplementary
- Citations:
- Appears in Collections:
Article: Two distinct pathways leading to nuclear apoptosis
Title | Two distinct pathways leading to nuclear apoptosis |
---|---|
Authors | |
Keywords | Apoptosis-inducing factor Caspases Apaf-1 Caspase-activated DNase Chromatin condensation |
Issue Date | 2000 |
Citation | Journal of Experimental Medicine, 2000, v. 192, n. 4, p. 571-580 How to Cite? |
Abstract | Apaf-1(-/-) or caspase-3(-/-) cells treated with a variety of apoptosis inducers manifest apoptosis-associated alterations including the translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, large scale DNA fragmentation, and initial chromatin condensation (stage I). However, when compared with normal control cells, Apaf-1(-/-) or caspase-3(-/-) cells fail to exhibit oligonucleosomal chromatin digestion and a more advanced pattern of chromatin condensation (stage II). Microinjection of such cells with recombinant AIF only causes peripheral chromatin condensation (stage I), whereas microinjection with activated caspase-3 or its down-stream target caspase-activated DNAse (CAD) causes a more pronounced type of chromatin condensation (stage II). Similarly, when added to purified HeLa nuclei, AIF causes stage I chromatin condensation and large-scale DNA fragmentation, whereas CAD induces stage II chromatin condensation and oligonucleosomal DNA degradation. Furthermore, in a cell-free system, concomitant neutralization of AIF and CAD is required to suppress the nuclear DNA loss caused by cytoplasmic extracts from apoptotic wild-type cells. In contrast, AIF depletion alone suffices to suppress the nuclear DNA loss contained in extracts from apoptotic Apaf-1(-/-) or caspase-3(-/-) cells. As a result, at least two redundant parallel pathways may lead to chromatin processing during apoptosis. One of these pathways involves Apaf-1 and caspases, as well as CAD, and leads to oligonucleosomal DNA fragmentation and advanced chromatin condensation. The other pathway, which is caspase-independent, involves AIF and leads to large-scale DNA fragmentation and peripheral chromatin condensation. |
Persistent Identifier | http://hdl.handle.net/10722/291547 |
ISSN | 2023 Impact Factor: 12.6 2023 SCImago Journal Rankings: 6.838 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Susin, Santos A. | - |
dc.contributor.author | Daugas, Eric | - |
dc.contributor.author | Ravagnan, Luigi | - |
dc.contributor.author | Samejima, Kumiko | - |
dc.contributor.author | Zamzami, Naoufal | - |
dc.contributor.author | Loeffler, Markus | - |
dc.contributor.author | Costantini, Paola | - |
dc.contributor.author | Ferri, Karine F. | - |
dc.contributor.author | Irinopoulou, Theano | - |
dc.contributor.author | Prévost, Marie Christine | - |
dc.contributor.author | Brothers, Greg | - |
dc.contributor.author | Mak, Tak W. | - |
dc.contributor.author | Penninger, Josef | - |
dc.contributor.author | Earnshaw, William C. | - |
dc.contributor.author | Kroemer, Guido | - |
dc.date.accessioned | 2020-11-17T14:54:36Z | - |
dc.date.available | 2020-11-17T14:54:36Z | - |
dc.date.issued | 2000 | - |
dc.identifier.citation | Journal of Experimental Medicine, 2000, v. 192, n. 4, p. 571-580 | - |
dc.identifier.issn | 0022-1007 | - |
dc.identifier.uri | http://hdl.handle.net/10722/291547 | - |
dc.description.abstract | Apaf-1(-/-) or caspase-3(-/-) cells treated with a variety of apoptosis inducers manifest apoptosis-associated alterations including the translocation of apoptosis-inducing factor (AIF) from mitochondria to nuclei, large scale DNA fragmentation, and initial chromatin condensation (stage I). However, when compared with normal control cells, Apaf-1(-/-) or caspase-3(-/-) cells fail to exhibit oligonucleosomal chromatin digestion and a more advanced pattern of chromatin condensation (stage II). Microinjection of such cells with recombinant AIF only causes peripheral chromatin condensation (stage I), whereas microinjection with activated caspase-3 or its down-stream target caspase-activated DNAse (CAD) causes a more pronounced type of chromatin condensation (stage II). Similarly, when added to purified HeLa nuclei, AIF causes stage I chromatin condensation and large-scale DNA fragmentation, whereas CAD induces stage II chromatin condensation and oligonucleosomal DNA degradation. Furthermore, in a cell-free system, concomitant neutralization of AIF and CAD is required to suppress the nuclear DNA loss caused by cytoplasmic extracts from apoptotic wild-type cells. In contrast, AIF depletion alone suffices to suppress the nuclear DNA loss contained in extracts from apoptotic Apaf-1(-/-) or caspase-3(-/-) cells. As a result, at least two redundant parallel pathways may lead to chromatin processing during apoptosis. One of these pathways involves Apaf-1 and caspases, as well as CAD, and leads to oligonucleosomal DNA fragmentation and advanced chromatin condensation. The other pathway, which is caspase-independent, involves AIF and leads to large-scale DNA fragmentation and peripheral chromatin condensation. | - |
dc.language | eng | - |
dc.relation.ispartof | Journal of Experimental Medicine | - |
dc.subject | Apoptosis-inducing factor | - |
dc.subject | Caspases | - |
dc.subject | Apaf-1 | - |
dc.subject | Caspase-activated DNase | - |
dc.subject | Chromatin condensation | - |
dc.title | Two distinct pathways leading to nuclear apoptosis | - |
dc.type | Article | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1084/jem.192.4.571 | - |
dc.identifier.pmid | 10952727 | - |
dc.identifier.pmcid | PMC2193229 | - |
dc.identifier.scopus | eid_2-s2.0-0034698733 | - |
dc.identifier.volume | 192 | - |
dc.identifier.issue | 4 | - |
dc.identifier.spage | 571 | - |
dc.identifier.epage | 580 | - |
dc.identifier.isi | WOS:000089067600013 | - |
dc.identifier.issnl | 0022-1007 | - |