rdf:type |
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lifeskim:mentions |
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pubmed:issue |
26
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pubmed:dateCreated |
2009-7-1
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pubmed:abstractText |
The inner membrane of the nuclear envelope (NE) was previously shown to contain a Na/Ca exchanger (NCX) tightly linked to GM1 ganglioside that mediates transfer of nucleoplasmic Ca(2+) to the NE lumen and constitutes a cytoprotective mechanism. This transfer was initially observed with isolated nuclei and is now demonstrated in living cells in relation to subcellular Ca(2+) dynamics. Four cell lines with varying expression of NCX and GM1 in the NE were transfected with cameleon-fluorescent Ca(2+) indicators genetically targeted to NE/endoplasmic reticulum (ER) and nucleoplasm to monitor [Ca(2+)](ne/er) and [Ca(2+)](n) respectively. Cytosolic Ca(2+) ([Ca(2+)](cyt)) was indicated with fura-2. Thapsigargin caused progressive loss of [Ca(2+)](ne/er), which was rapidly replaced on addition of extrinsic Ca(2+) to those cells containing fully functional NCX/GM1: differentiated NG108-15 and C6 cells. Reduced elevation of [Ca(2+)](ne/er) following thapsigargin depletion occurred in cells containing little or no GM1 in the NE: undifferentiated NG108-15 and NG-CR72 cells. No change in [Ca(2+)](ne/er) due to applied Ca(2+) was seen in Jurkat cells, which entirely lack NCX. Ca(2+) entry to NE/ER was also blocked by KB-R7943, inhibitor of NCX. [Ca(2+)](n) and [Ca(2+)](cyt) were elevated independent of [Ca(2+)](ne/er) and remained in approximate equilibrium with each other. Ca(2+) rise in the ER originated in the NE region and extended to the entire ER network. These results indicate the nuclear NCX/GM1 complex acts to gate Ca(2+) transfer from cytosol to ER, an alternate route to the sarcoplasmic/endoplasmic reticulum calcium ATPase pump. They also suggest a possible contributory mechanism for independent regulation of nuclear Ca(2+).
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19541636-10051607,
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1091-6490
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
30
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pubmed:volume |
106
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10829-34
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:19541636-Active Transport, Cell Nucleus,
pubmed-meshheading:19541636-Animals,
pubmed-meshheading:19541636-Calcium,
pubmed-meshheading:19541636-Cell Differentiation,
pubmed-meshheading:19541636-Cell Line, Tumor,
pubmed-meshheading:19541636-Cell Nucleus,
pubmed-meshheading:19541636-Cytosol,
pubmed-meshheading:19541636-Endoplasmic Reticulum,
pubmed-meshheading:19541636-G(M1) Ganglioside,
pubmed-meshheading:19541636-Humans,
pubmed-meshheading:19541636-Hybrid Cells,
pubmed-meshheading:19541636-Immunoblotting,
pubmed-meshheading:19541636-Immunohistochemistry,
pubmed-meshheading:19541636-Ion Transport,
pubmed-meshheading:19541636-Jurkat Cells,
pubmed-meshheading:19541636-Microscopy, Fluorescence,
pubmed-meshheading:19541636-Nuclear Envelope,
pubmed-meshheading:19541636-Sodium-Calcium Exchanger,
pubmed-meshheading:19541636-Thiourea
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pubmed:year |
2009
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pubmed:articleTitle |
Sodium-calcium exchanger complexed with GM1 ganglioside in nuclear membrane transfers calcium from nucleoplasm to endoplasmic reticulum.
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pubmed:affiliation |
Department of Neurology and Neurosciences, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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