Source:http://linkedlifedata.com/resource/pubmed/id/15229105
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rdf:type | |
lifeskim:mentions |
umls-concept:C0001455,
umls-concept:C0017262,
umls-concept:C0034052,
umls-concept:C0086418,
umls-concept:C0127400,
umls-concept:C0185117,
umls-concept:C0441655,
umls-concept:C0871261,
umls-concept:C1135918,
umls-concept:C1156237,
umls-concept:C1421171,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911684,
umls-concept:C2911692
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pubmed:issue |
5
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pubmed:dateCreated |
2004-10-11
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pubmed:abstractText |
Extracellular ATP and intracellular cyclic AMP response element-binding protein (CREB, a transcription factor) promote cell proliferation in many cell types. The canonical transient receptor potential (TRPC) channels, which putatively participate in forming store- and receptor-operated Ca2+ channels, have been implicated in the pulmonary vascular remodeling processes. A link between extracellular ATP, CREB activation, and TRPC4 channel expression and activity has not been shown in human pulmonary artery smooth muscle cells (PASMC). Long-term (24-48 h) treatment of human PASMC with a low dose (100 microM) of ATP, which did not trigger a transient rise in free cytosolic Ca2+ concentration ([Ca2+]i) when applied acutely to the cells, caused marked increases in CREB phosphorylation and TRPC4 protein expression. The time course indicated that the ATP-mediated CREB phosphorylation preceded TRPC4 upregulation, whereas transfection of a nonphosphorylatable CREB mutant abolished ATP-mediated TRPC4 expression. Furthermore, treatment of human PASMC with ATP also enhanced the amplitude of capacitative Ca2+ entry (CCE) induced by passive store depletion, whereas the small interfering RNA specifically targeting TRPC4 attenuated ATP-mediated increases in TRPC4 expression and CCE amplitude and inhibited ATP-induced PASMC proliferation. These data suggest that low-dose ATP exerts part of its mitogenic effect in human PASMC via CREB-mediated upregulation of TRPC4 channel expression and activity and the subsequent increase in CCE and [Ca2+]i.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/TRPC Cation Channels
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0363-6143
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
287
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C1192-201
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15229105-Adenosine Triphosphate,
pubmed-meshheading:15229105-Animals,
pubmed-meshheading:15229105-Calcium,
pubmed-meshheading:15229105-Calcium Channels,
pubmed-meshheading:15229105-Cell Division,
pubmed-meshheading:15229105-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:15229105-Cytoplasm,
pubmed-meshheading:15229105-Dose-Response Relationship, Drug,
pubmed-meshheading:15229105-Humans,
pubmed-meshheading:15229105-Muscle, Smooth, Vascular,
pubmed-meshheading:15229105-Myocytes, Smooth Muscle,
pubmed-meshheading:15229105-Phosphorylation,
pubmed-meshheading:15229105-Pulmonary Artery,
pubmed-meshheading:15229105-TRPC Cation Channels,
pubmed-meshheading:15229105-Time Factors
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pubmed:year |
2004
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pubmed:articleTitle |
ATP-induced mitogenesis is mediated by cyclic AMP response element-binding protein-enhanced TRPC4 expression and activity in human pulmonary artery smooth muscle cells.
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pubmed:affiliation |
Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0725, USA. xiyuan@ucsd.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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