| http://purl.uniprot.org/citations/21525433 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21525433 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21525433 | http://www.w3.org/2000/01/rdf-schema#comment | "Chronic hypoxia (CH) activates the Ca(2+)-dependent transcription factor nuclear factor of activated T cells isoform c3 (NFATc3) in mouse pulmonary arteries. However, the mechanism of this response has not been explored. Since we have demonstrated that NFATc3 is required for CH-induced pulmonary arterial remodeling, establishing how CH activates NFATc3 is physiologically significant. The goal of this study was to test the hypothesis that endothelin-1 (ET-1) contributes to CH-induced NFATc3 activation. We propose that this mechanism requires increased pulmonary arterial smooth muscle cell (PASMC) intracellular Ca(2+) concentration ([Ca(2+)](i)) and stimulation of RhoA/Rho kinase (ROK), leading to calcineurin activation and actin cytoskeleton polymerization, respectively. We found that: 1) CH increases pulmonary arterial pre-pro-ET-1 mRNA expression and lung RhoA activity; 2) inhibition of ET receptors, calcineurin, L-type Ca(2+) channels, and ROK blunts CH-induced NFATc3 activation in isolated intrapulmonary arteries from NFAT-luciferase reporter mice; and 3) both ET-1-induced NFATc3 activation in isolated mouse pulmonary arteries ex vivo and ET-1-induced NFATc3-green fluorescence protein nuclear import in human PASMC depend on ROK and actin polymerization. This study suggests that CH increases ET-1 expression, thereby elevating PASMC [Ca(2+)](i) and RhoA/ROK activity. As previously demonstrated, elevated [Ca(2+)](i) is required to activate calcineurin, which dephosphorylates NFATc3, allowing its nuclear import. Here, we demonstrate that ROK increases actin polymerization, thus providing structural support for NFATc3 nuclear transport."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00029.2011"xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.org/dc/terms/identifier | "doi:10.1152/ajpcell.00029.2011"xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Bosc L.V."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Bosc L.V."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Diaz J.M."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Diaz J.M."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Nitta C.H."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Nitta C.H."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Sherpa M.L."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "Sherpa M.L."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "de Frutos S."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/author | "de Frutos S."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/name | "Am. J. Physiol."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/name | "Am. J. Physiol."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/pages | "C441-C450"xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/pages | "C441-C450"xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/title | "Endothelin-1 contributes to increased NFATc3 activation by chronic hypoxia in pulmonary arteries."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/title | "Endothelin-1 contributes to increased NFATc3 activation by chronic hypoxia in pulmonary arteries."xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/volume | "301"xsd:string |
| http://purl.uniprot.org/citations/21525433 | http://purl.uniprot.org/core/volume | "301"xsd:string |