Thromboxane A2 receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells

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dc.contributor.author Miggin, Sinead M.
dc.contributor.author Kinsella, B. Therese
dc.date.accessioned 2011-09-22T13:26:58Z
dc.date.available 2011-09-22T13:26:58Z
dc.date.copyright 2001 Elsevier B.V. en
dc.date.issued 2001-05-28
dc.identifier.citation Biochimica et Biophysica Acta (BBA) - Molecular Cell Research en
dc.identifier.issn 0167-4889
dc.identifier.uri http://hdl.handle.net/10197/3163
dc.description.abstract Both thromboxane (TX) A2 and 8-epi prostaglandin (PG) F2alpha have been reported to stimulate mitogenesis of vascular smooth muscle (SM) in a number of species. However, TXA2 and 8-epiPGF2alpha mediated mitogenic signalling have not been studied in detail in human vascular SM. Thus, using the human uterine ULTR cell line as a model, we investigated TXA2 receptor (TP) mediated mitogenic signalling in cultured human vascular SM cells. Both the TP agonist U46619 and 8-epiPGF2alpha elicited time and concentration dependent activation of the extracellular signal regulated kinase (ERK)s and c-Jun N-terminal kinase (JNK)s in ULTR cells. Whereas the TP antagonist SQ29,548 abolished U46619-mediated signalling, it only partially inhibited 8-epiPGF2alpha mediated ERK and JNK activation in ULTR cells. Both U46619 and 8-epiPGF2alpha induced ERK activations were inhibited by the protein kinase (PK) C, PKA and phosphoinositide 3-kinase inhibitors GF 109203X, H-89 and wortmannin, respectively, but were unaffected by pertussis toxin. In addition, U46619 mediated ERK activation in ULTR cells involves transactivation of the EGF receptor. In humans, TXA2 signals through two distinct TP isoforms. In investigating the involvement of the TP isoforms in mitogenic signalling, both TPalpha and TPbeta, independently directed U46619 and 8-epiPGF2alpha mediated ERK and JNK activation in human embryonic kidney (HEK) 293 cells over-expressing the individual TP isoforms. However, in contrast to that which occurred in ULTR cells, SQ29,548 abolished 8-epiPGF2alpha mediated ERK and JNK activation through both TPalpha and TPbeta in HEK 293 cells providing further evidence that 8-epiPGF2alpha may signal through alternative receptors, in addition to the TPs, in human uterine ULTR cells. en
dc.description.sponsorship Health Research Board en
dc.format.extent 1419877 bytes
dc.format.mimetype application/pdf
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.requires Biomolecular and Biomedical Science Research Collection en
dc.relation.requires Conway Institute Research Collection en
dc.rights This is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research Volume 1539, Issues 1-2, 28 May 2001, Pages 147-162 DOI 10.1016/S0167-4889(01)00103-3. en
dc.subject Thromboxane A2 receptor en
dc.subject TPalpha en
dc.subject TPbeta en
dc.subject 8-epiPGF2alpha en
dc.subject Smooth muscle en
dc.subject MAPK en
dc.subject ERK en
dc.subject JNK en
dc.subject Mitogenesis en
dc.subject.lcsh Thromboxanes en
dc.subject.lcsh Smooth muscle en
dc.subject.lcsh Mitogen-activated protein kinases en
dc.subject.lcsh Protein kinases en
dc.subject.lcsh Mitogens en
dc.subject.mesh Receptors, Thromboxane A2, Prostaglandin H2 en
dc.subject.mesh 8-epi-prostaglandin F2alpha en
dc.subject.mesh Muscle, Smooth en
dc.subject.mesh Mitogen-Activated Protein Kinases en
dc.subject.mesh Mitogens en
dc.title Thromboxane A2 receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells en
dc.type Journal Article en
dc.internal.availability Full text available en
dc.internal.webversions Publisher's version en
dc.internal.webversions http://dx.doi.org/10.1016/S0167-4889(01)00103-3 en
dc.status Peer reviewed en
dc.identifier.volume 1539 en
dc.identifier.issue 1-2 en
dc.identifier.startpage 147 en
dc.identifier.endpage 162 en
dc.identifier.doi 10.1016/S0167-4889(01)00103-3
dc.neeo.contributor Miggin|Sinead M.|aut| en
dc.neeo.contributor Kinsella|B. Therese|aut| en
dc.description.othersponsorship Wellcome Trust en
dc.description.othersponsorship Irish Heart Foundation en
dc.description.othersponsorship Enterprise Ireland en
dc.description.admin ke,ti, -SB01/09/2011 en


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