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dc.contributor.author Abrenica, B
dc.contributor.author Pierce, GN
dc.contributor.author Gilchrist, JSC
dc.date.accessioned 2007-10-09T18:43:57Z
dc.date.available 2007-10-09T18:43:57Z
dc.date.issued 2003-09-30
dc.identifier.citation CAN J EARTH SCI, SEP 2003, vol. 40, no. 9, p.1259 to 1278. en
dc.identifier.uri http://hdl.handle.net/1993/2915
dc.description.abstract In this study, we investigated whether nucleoplasmic free Ca2+ in aortic vascular smooth muscle cells (VSMCs) might be independently regulated from cytosolic free Ca2+. Understanding mechanisms and pathways responsible for this regulation is especially relevant given the role of a numerous intranuclear Ca2+-sensitive proteins in transcriptional regulation, apoptosis and cell division. The question of an independent regulatory mechanism remains largely unsettled because the previous use of intensitometric fluorophores (e.g., Fluo-3) has been criticized on technical grounds. To circumvent the potential problem of fluorescence artifact, we utilized confocal laser scanning microscopy to image intracellular Ca2+ movements with the ratiometric fluorophore Indo-1. In cultured rabbit VSMCs, we found sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA) pumps and ryanodine receptor (RyR) Ca2+ channel proteins to be discretely arranged within a perinuclear locus, as determined by fluorescent staining patterns of BODIPY(R) FL thapsigargin and BODIPY(R) FL-X Ry. When intracellular Ca2+ stores were mobilized by addition of thapsigargin (5 muM) and activatory concentrations of ryanodine (1 muM), Indo-1 ratiometric signals were largely restricted to the nucleoplasm. Cytosolic signals, by comparison, were relatively small and even then its spatial distribution was largely perinuclear rather homogeneous. These observations indicate perinuclear RyR and SERCA proteins are intimately involved in regulating VSMC nucleoplasmic Ca2+ concentrations. We also observed a similar pattern of largely nucleoplasmic Ca2+ mobilization upon exposure of cells to the immunosuppressant drug FK506 (tacrolimus), which binds to the RyR-associated immunophillin-binding proteins FKBP12 and FKBP12.6. However, initial FK506-induced nucleoplasmic Ca2+ mobilization was followed by marked reduction of Indo-1 signal intensity close to pretreatment levels. This suggested FK506 exerts both activatory and inhibitory effects upon RyR channels. The latter was reinforced by observed effects of FK506 to only reduce nucleoplasmic Indo-1 signal intensity when added following pretreatment with both activatory and inhibitory concentrations of ryanodine. These latter observations raise the possibility that VSMC nuclei represent an important sink of intracellular Ca2+ and may help explain vasodilatory actions of FK506 observed by others. en
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dc.language.iso en_US
dc.rights No part of the NRC Research Press electronic journals may be reproduced, stored, or transmitted in any form or by any means, without the written permission of the publisher, except as stated below. Under the Canadian Copyright Act, individuals may download or print single copies of articles for personal research or study. Any person may reproduce short excerpts from articles in the journals for any purpose that respects the moral rights of authors, provided that the source is fully acknowledged. As a courtesy, the consent of authors of such material should be obtained directly from the author. Authorization to reproduce items for other than personal research or study, as stated above, may be obtained via Access © upon payment of the copyright fee of $10.00 per copy. NRC Research Press also extends certain additional rights to authors. The above rights do not extend to copying or reproduction for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. For such copying or reproduction, arrangements must be made with NRC Research Press. en
dc.rights info:eu-repo/semantics/restrictedAccess
dc.subject LAURENTIDE ICE-SHEET en
dc.subject ABRUPT CLIMATE-CHANGE en
dc.subject C-14 YR BP en
dc.subject 3-OUTLET CONTROL en
dc.subject LARGE BEACHES en
dc.subject VOLUME en
dc.subject BASIN en
dc.subject SEDIMENTATION en
dc.subject SASKATCHEWAN en
dc.subject BATHYMETRY en
dc.title Nucleoplasmic calcium regulation in rabbit aortic vascular smooth muscle cells en
dc.status Peer reviewed en
dc.identifier.doi http://dx.doi.org/10.1139/y03-005
dc.identifier.doi http://dx.doi.org/10.1139/y03-005


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