Linked Life Data

16815889

Source:http://linkedlifedata.com/resource/pubmed/id/16815889

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2006-10-10
pubmed:abstractText
Activity of voltage-gated K(+) (K(V)) channels in pulmonary artery smooth muscle cells (PASMC) plays an important role in control of apoptosis and proliferation in addition to regulating membrane potential and pulmonary vascular tone. Bone morphogenetic proteins (BMPs) inhibit proliferation and induce apoptosis in normal human PASMC, whereas dysfunctional BMP signaling and downregulated K(V) channels are involved in pulmonary vascular medial hypertrophy associated with pulmonary hypertension. This study evaluated the effect of BMP-2 on K(V) channel function and expression in normal human PASMC. BMP-2 (100 nM for 18-24 h) significantly (>2-fold) upregulated mRNA expression of KCNA5, KCNA7, KCNA10, KCNC3, KCNC4, KCNF1, KCNG3, KCNS1, and KCNS3 but downregulated (at least 2-fold) KCNAB1, KCNA2, KCNG2, and KCNV2. The most dramatic change was the >10-fold downregulation of KCNG2 and KCNV2, two electrically silent gamma-subunits that form heterotetramers with functional K(V) channel alpha-subunits (e.g., KCNB1-2). Furthermore, the amplitude and current density of whole cell K(V) currents were significantly increased in PASMC treated with BMP-2. It has been demonstrated that K(+) currents generated by KCNB1 and KCNG1 (or KCNG2) or KCNB1 and KCNV2 heterotetramers are smaller than those generated by KCNB1 homotetramers, indicating that KCNG2 and KCNV2 (2 subunits that were markedly downregulated by BMP-2) are inhibitors of functional K(V) channels. These results suggest that BMP-2 divergently regulates mRNA expression of various K(V) channel alpha-, beta-, and gamma-subunits and significantly increases whole cell K(V) currents in human PASMC. Finally, we present evidence that attenuation of c-Myc expression by BMP-2 may be involved in BMP-2-mediated increase in K(V) channel activity and regulation of K(V) channel expression. The increased K(V) channel activity may be involved in the proapoptotic and/or antiproliferative effects of BMP-2 on PASMC.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1040-0605
pubmed:author
pubmed:issnType
Print
pubmed:volume
291
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L993-1004
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:16815889-Apoptosis, pubmed-meshheading:16815889-Bone Morphogenetic Protein 2, pubmed-meshheading:16815889-Bone Morphogenetic Proteins, pubmed-meshheading:16815889-Cells, Cultured, pubmed-meshheading:16815889-Gene Expression, pubmed-meshheading:16815889-Humans, pubmed-meshheading:16815889-Hypertension, Pulmonary, pubmed-meshheading:16815889-Membrane Potentials, pubmed-meshheading:16815889-Muscle, Smooth, Vascular, pubmed-meshheading:16815889-Patch-Clamp Techniques, pubmed-meshheading:16815889-Potassium, pubmed-meshheading:16815889-Potassium Channels, Voltage-Gated, pubmed-meshheading:16815889-Protein Subunits, pubmed-meshheading:16815889-Proto-Oncogene Proteins c-myc, pubmed-meshheading:16815889-Pulmonary Artery, pubmed-meshheading:16815889-RNA, Messenger, pubmed-meshheading:16815889-Transforming Growth Factor beta, pubmed-meshheading:16815889-Up-Regulation
pubmed:year
2006
pubmed:articleTitle
Bone morphogenetic protein-2 upregulates expression and function of voltage-gated K+ channels in human pulmonary artery smooth muscle cells.
pubmed:affiliation
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Diego, 9500 Gilman Drive, MC 0725, La Jolla, 92093-0725, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural