FasL-Triggered Death of Jurkat Cells Requires Caspase 8-Induced, ATP-Dependent Cross-Talk Between Fas and the Purinergic Receptor P2X7
Author
dc.contributor.author
Aguirre, Adam
Author
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Shoji, Kenji F.
es_CL
Author
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Sáez, Juan C.
es_CL
Author
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Henríquez Luna, Mauricio
es_CL
Author
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Quest, Andrew F. G.
es_CL
Admission date
dc.date.accessioned
2014-01-31T18:46:30Z
Available date
dc.date.available
2014-01-31T18:46:30Z
Publication date
dc.date.issued
2013
Cita de ítem
dc.identifier.citation
J. Cell. Physiol. 228: 485–493, 2013
en_US
Identifier
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DOI: 10.1002/jcp.24159
Identifier
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https://repositorio.uchile.cl/handle/2250/129240
General note
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Artículo de publicación ISI
en_US
Abstract
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Fas ligation via the ligand FasL activates the caspase-8/caspase-3-dependent extrinsic death pathway. In so-called type II cells, an additional
mechanism involving tBid-mediated caspase-9 activation is required to efficiently trigger cell death. Other pathways linking FasL–Fas
interaction to activation of the intrinsic cell death pathway remain unknown. However, ATP release and subsequent activation of
purinergic P2X7 receptors (P2X7Rs) favors cell death in some cells. Here, we evaluated the possibility that ATP release downstream of
caspase-8 via pannexin1 hemichannels (Panx1 HCs) and subsequent activation of P2X7Rs participate in FasL-stimulated cell death. Indeed,
upon FasL stimulation, ATP was released from Jurkat cells in a time- and caspase-8-dependent manner. Fas and Panx1 HCs colocalized and
inhibition of the latter, but not connexin hemichannels, reduced FasL-induced ATP release. Extracellular apyrase, which hydrolyzes ATP,
reduced FasL-induced death. Also, oxidized-ATP or Brilliant Blue G, two P2X7R blockers, reduced FasL-induced caspase-9 activation and
cell death. These results represent the first evidence indicating that the two death receptors, Fas and P2X7R connect functionally via
caspase-8 and Panx1 HC-mediated ATP release to promote caspase-9/caspase-3-dependent cell death in lymphoid cells. Thus, a hitherto
unsuspected route was uncovered connecting the extrinsic to the intrinsic pathway to amplify death signals emanating from the Fas
receptor in type II cells.
en_US
Patrocinador
dc.description.sponsorship
This work was
supported by FONDECYT-FONDAP (to A.F.G. Quest)
15010006, FONDECYT (to A.F.G. Quest) 1090071,
FONDECYT-Postdoctoral fellowship (to M. Henriquez)
3070045, and ANILLO (to J.C. Sa´ez) ACT-71.