|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
11
|
|
pubmed:dateCreated |
2003-5-21
|
|
pubmed:abstractText |
In response to ATP binding, the P2X7R facilitates cation channel activation, nonspecific pore formation, rapid changes in plasma membrane morphology, and secretion of IL-1 beta from LPS-primed macrophages. To investigate the relationship between the P2X7R-dependent changes in plasma membrane organization and the release of IL-1 beta, we generated time-lapse movies of ATP-stimulated BAC1 murine macrophages in conjunction with biochemical analyses of IL-1 beta release. Similar image analyses in human embryonic kidney 293 cells expressing recombinant P2X7R (HEK-P2X7) permitted comparison of P2X7R-dependent effects in macrophage vs nonmacrophage backgrounds. Whereas HEK-P2X7 cells exhibit zeiotic blebbing within 5 min of ATP treatment, BAC1 macrophages initiated a distinct "tethered" blebbing 10 min after ATP addition. This blebbing was comparably induced by the P2X7R-selective agonist BzATP and was blocked by P2X7R inhibitors KN-62 and oxidized ATP. Blebbing was initiated at ATP concentrations > or = 3 mM, but optimal IL-1 beta release occurred at 1 mM ATP. P2X7R-dependent blebbing was abrogated in the presence of Rho-effector kinase inhibitors Fasudil and Y-27632, but ATP-induced IL-1 beta release was unaffected. ATP-induced activation of RhoA could be detected in both HEK-P2X7 cells and BAC1 murine macrophages. Thus, P2X7R activation signals distinct, novel membrane blebbing events (dependent on RhoA activation and Rho-effector kinase activity) and simultaneously initiates release of IL-1 beta. Our observations that blebbing and IL-1 beta release are dissociable suggest these events occur via parallel rather than convergent signaling pathways.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
AIM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-(5-Isoquinolinesulfonyl)-2-Methylp...,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/P2RX7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/P2rx7 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2X7,
http://linkedlifedata.com/resource/pubmed/chemical/Y 27632,
http://linkedlifedata.com/resource/pubmed/chemical/fasudil,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/rhoA GTP-Binding Protein
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jun
|
|
pubmed:issn |
0022-1767
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
1
|
|
pubmed:volume |
170
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
5728-38
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:12759456-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine,
pubmed-meshheading:12759456-Adenosine Triphosphate,
pubmed-meshheading:12759456-Amides,
pubmed-meshheading:12759456-Animals,
pubmed-meshheading:12759456-Caspases,
pubmed-meshheading:12759456-Cell Line,
pubmed-meshheading:12759456-Enzyme Activation,
pubmed-meshheading:12759456-Extracellular Space,
pubmed-meshheading:12759456-Humans,
pubmed-meshheading:12759456-Interleukin-1,
pubmed-meshheading:12759456-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:12759456-Macrophages,
pubmed-meshheading:12759456-Mice,
pubmed-meshheading:12759456-Protein-Serine-Threonine Kinases,
pubmed-meshheading:12759456-Pseudopodia,
pubmed-meshheading:12759456-Pyridines,
pubmed-meshheading:12759456-Receptors, Purinergic P2,
pubmed-meshheading:12759456-Receptors, Purinergic P2X7,
pubmed-meshheading:12759456-Signal Transduction,
pubmed-meshheading:12759456-rho-Associated Kinases,
pubmed-meshheading:12759456-rhoA GTP-Binding Protein
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
P2X7 receptor-dependent blebbing and the activation of Rho-effector kinases, caspases, and IL-1 beta release.
|
|
pubmed:affiliation |
Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
|
