Linked Life Data

19570880

Source:http://linkedlifedata.com/resource/pubmed/id/19570880

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-8-20
pubmed:abstractText
Extracellular ATP regulates many physiological processes via release of nitric oxide (NO). ATP stimulates NO in thick ascending limbs (TALs), but the signaling cascade involved in the cells of this nephron segment, as well as many other types of cells, is poorly understood. We hypothesized that ATP enhances NO synthase (NOS) activity by stimulating PI3 kinase and Akt. We measured 1) NO in TALs using the NO-sensitive dye DAF-2 DA and 2) Akt activity by fluorescence resonance energy transfer and phosphorylation of Akt isoforms. ATP (100 microM) stimulated NO in wild-type mice [26 +/- 4 arbitrary units (AU)], but not in NOS3 -/- mice (2 +/- 2 AU; P < 0.04). In the presence of the NOS1- and NOS2-selective inhibitors 7-NI and 1400W, ATP stimulated NO by 30 +/- 2 and 33 +/- 3 AU, respectively (not significant vs. control). In the presence of the PI3 kinase inhibitor LY294002, ATP-increased NO was reduced by 85% (5 +/- 2 vs. 28 +/- 4 AU; P < 0.02). ATP alone increased Akt activity and this effect was significantly blocked by suramin, a P2 receptor antagonist. In the presence of an Akt-selective inhibitor, ATP-induced NO was blocked by 90 +/- 4%. ATP significantly stimulated Akt1 phosphorylation at Ser(473) by 91 +/- 13%, whereas Akt2 phosphorylation remained unchanged and Akt3 phosphorylation decreased. In vivo transduction of TALs with a dominant-negative Akt1 significantly decreased ATP-induced NO by 88 +/- 6%. We concluded that ATP increases NOS3-derived NO via Akt1 activation in the TAL.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide, http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type III, http://linkedlifedata.com/resource/pubmed/chemical/Nos3 protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Nos3 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Purinergic P2
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F646-52
pubmed:dateRevised
2011-7-14
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Akt1 mediates purinergic-dependent NOS3 activation in thick ascending limbs.
pubmed:affiliation
Division of Hypertension and Vascular Research, Henry Ford Hospital, 2799 W. Grand Boulevard, Detroit, MI 48202, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural