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Angiotensin II AT1 receptor internalization, translocation and de novo synthesis modulate cytosolic and nuclear calcium in human vascular smooth muscle cells

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dc.contributor.author Sleiman, S.
dc.contributor.author Bkaily, G.
dc.contributor.author Stephan, J.
dc.contributor.author Asselin, C.
dc.contributor.author Choufani, S.
dc.contributor.author Kamal, M.
dc.contributor.author Jacques, D.
dc.contributor.author Gobeil, F.
dc.contributor.author D'Orleans-Juste, P.
dc.date.accessioned 2017-09-06T09:54:10Z
dc.date.available 2017-09-06T09:54:10Z
dc.date.copyright 2003 en_US
dc.identifier.issn 1205-7541 en_US
dc.identifier.uri http://hdl.handle.net/10725/6146
dc.description.abstract The present study was designed to verify if human (h) Angiotensin II (Ang II) type-1 receptor (hAT1R) undergoes internalization, nuclear translocation, and de novo synthesis in primary culture of human aortic vascular smooth muscle cells (hVSMCs) and if overexpression of this receptor modulates sustained free cytosolic ([Ca]c) and nuclear ([Ca]n) calcium. 3-dimensional (3-D) confocal microscopy was used to monitor free intracellular Ca2+ and hAT1R-green fluorescence protein (GFP) fusion protein in cultured hVSMCs. Immunofluorescence studies showed the presence of hAT1R and the absence of hAT2R in normal hVSMCs. Using 3-D imaging technique, hAT1 receptors were localized at the sarcolemma and in the cytosolic and nuclear compartments. In native as well as in normal hAT1R or hAT1R GFP overexpressing hVSMCs, Ang II (10 9 and 10 4 M) induced internalization and nuclear translocation of this type of receptor. The internalization of hAT1Rs is mediated via clathrin-coated pits and vesicles pathway. This phenomenon of trancellular trafficking of receptors was associated with an increase of hAT1R. The Ang II induced increase of hAT1R density was prevented by the protein synthesis inhibitor cycloheximide. Overexpression of hAT1R and hAT1R GFP decreased both basal cytosolic and nuclear Ca2+. In normal hVSMCs and low hAT1R GFP overexpressing hVSMCs, Ang II (10 15 to 10 4 M) induced a dose-dependent sustained increase of [Ca]c and [Ca]n with an EC50 near 5 × 10 11 and 5 × 10 9 M, respectively. Our results suggest that hAT1Rs are the predominant type of Ang II receptors in aortic hVSMCs and are present in the sarcolemma, the cytosolic and the nuclear compartments. Ang II rapidly induces hAT1R internalization, nuclear translocation, as well as nuclear de novo synthesis of this receptor. The hAT1R overexpression in hVSMCs modulates sustained [Ca]c and [Ca]n.Key words: angiotensin, calcium, protein synthesis, nucleus, AT1 receptor, nuclear de novo synthesis. en_US
dc.language.iso en en_US
dc.title Angiotensin II AT1 receptor internalization, translocation and de novo synthesis modulate cytosolic and nuclear calcium in human vascular smooth muscle cells en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SAS en_US
dc.author.idnumber 201408170 en_US
dc.author.department Natural Sciences en_US
dc.description.embargo N/A en_US
dc.relation.journal Canadian Journal of Physiology and Pharmacology en_US
dc.journal.volume 81 en_US
dc.journal.issue 3 en_US
dc.article.pages 274-287 en_US
dc.identifier.doi https://doi.org/10.1139/y03-007 en_US
dc.identifier.ctation Bkaily, G., Sleiman, S., Stephan, J., Asselin, C., Choufani, S., Kamal, M., ... & D'Orleans-Juste, P. (2003). Angiotensin II AT1 receptor internalization, translocation and de novo synthesis modulate cytosolic and nuclear calcium in human vascular smooth muscle cells. Canadian journal of physiology and pharmacology, 81(3), 274-287. en_US
dc.author.email sama.sleiman@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url http://www.nrcresearchpress.com/doi/abs/10.1139/y03-007#.Wa_ESsgjHcs en_US
dc.author.affiliation Lebanese American University en_US


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