Source:http://linkedlifedata.com/resource/pubmed/id/19166859
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
4
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pubmed:dateCreated |
2009-3-10
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pubmed:abstractText |
A polymorphism in the human Cx37 gene (C1019T), resulting in a non-conservative amino acid change in the regulatory C-terminus of the Cx37 protein (P319S), has been proposed as a prognostic marker for atherosclerosis. We have recently demonstrated that Cx37 hemichannels control the initiation of atherosclerotic plaque development by regulating ATP-dependent monocyte adhesion in atherosclerosis-susceptible apolipoprotein E-deficient mice. In this study, we have measured the electrical properties of Cx37 hemichannels (HCs) and gap junction channels (GJCs) with voltage-clamp methods. To this end, we have transfected hCx37-P319, hCx37-S319 or empty pIRES-eGFP vector cDNA into communication-deficient HeLa cells. In clones expressing similar levels of Cx37, exposure of single cells to low-Ca(2+) solution induced a voltage-sensitive HC current. The analysis yielded a bell-shaped function g(hc)=f(V(m)) (g(hc): normalized conductance at steady state; V(m): membrane potential) with a maximum around V(m)=-30 mV. The peak g(hc) of Cx37-P319 was 3-fold larger than that of Cx37-S319 HCs. Experiments on cell pairs revealed that Cx37-P319 GJCs exhibited a 1.5-fold larger unitary conductance than Cx37-S319 GJCs. Hence, the larger peak g(hc) of the former may reflect a larger conductance of their HCs. Using the same clones, we found that Cx37-P319 cells released more ATP and were less adhesive than Cx37-S319 cells. The reduction in adhesiveness of Cx37-expressing cells was prevented by extracellular apyrase. We conclude that the differences in biophysical properties between polymorphic HCs may be responsible for inequality in ATP release between Cx37-P319 and Cx37-S319 cells, which results in differential cell adhesion.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1095-8584
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
46
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
499-507
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pubmed:meshHeading |
pubmed-meshheading:19166859-Adenosine Triphosphate,
pubmed-meshheading:19166859-Cell Adhesion,
pubmed-meshheading:19166859-Connexins,
pubmed-meshheading:19166859-Electrophysiological Phenomena,
pubmed-meshheading:19166859-Gap Junctions,
pubmed-meshheading:19166859-HeLa Cells,
pubmed-meshheading:19166859-Humans,
pubmed-meshheading:19166859-Polymorphism, Genetic,
pubmed-meshheading:19166859-Transfection
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pubmed:year |
2009
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pubmed:articleTitle |
Functional differences between human Cx37 polymorphic hemichannels.
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pubmed:affiliation |
Department of Internal Medicine, Division of Cardiology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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