Linked Life Data

21430287

Source:http://linkedlifedata.com/resource/pubmed/id/21430287

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-6-28
pubmed:abstractText
To test the hypothesis that Na(+)/H(+) exchanger (NHE) regulatory factor 2 (NHERF2) is necessary for multiple aspects of acute regulation of NHE3 in intact mouse small intestine, distal ileal NHE3 activity was determined using two-photon microscopy/SNARF-4F in a NHERF2-null mouse model. The NHERF2-null mouse ileum had shorter villi, deeper crypts, and decreased epithelial cell number. Basal rates of NHE3 activity were reduced in NHERF2-null mice, which was associated with a reduced percentage of NHE3 in the apical domain and an increase in intracellular NHE3 amount but no change in total level of NHE3 protein. cAMP, cGMP, and elevated Ca(2+) due to apical exposure to UTP all inhibited NHE3 activity in wild-type mouse ileum but not in NHERF2-null mice, while inhibition by hyperosmolarity occurred normally. The cAMP-increased phosphorylation of NHE3 at aa 552; levels of PKAII? and cGMP-dependent protein kinase II (cGKII); and elevation of Ca(2+) were similar in wild-type and NHERF2-null mouse ileum. Luminal lysophosphatidic acid (LPA) stimulated NHE3 in wild-type but not in NHERF2-null ileum. In conclusion, 1) there are subtle structural abnormalities in the small intestine of NHERF2-null mouse which include fewer villus epithelial cells; 2) the decreased basal NHE3 activity and reduced brush border NHE3 amount in NHERF2-null mice show that NHERF2 is necessary for normal basal trafficking or retention of NHE3 in the apical domain; 3) hyperosmolar inhibition of NHE3 occurs similarly in wild-type and NHERF2-null ileum, demonstrating that some inhibitory mechanisms of NHE3 are not NHERF2 dependent; 4) cAMP inhibition of NHE3 is NHERF2 dependent at a step downstream of cAMP/PKAII phosphorylation of NHE3 at aa 552; 5) cGMP- and UTP-induced inhibition of NHE3 are NHERF2 dependent at steps beyond cGKII and the UTP-induced increase of intracellular Ca(2+); and 6) LPA stimulation of NHE3 is also NHERF2 dependent.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1522-1563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
301
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C126-36
pubmed:meshHeading
pubmed-meshheading:21430287-Animals, pubmed-meshheading:21430287-Calcium, pubmed-meshheading:21430287-Cell Proliferation, pubmed-meshheading:21430287-Cells, Cultured, pubmed-meshheading:21430287-Cyclic AMP, pubmed-meshheading:21430287-Cyclic GMP, pubmed-meshheading:21430287-Epithelial Cells, pubmed-meshheading:21430287-Ileum, pubmed-meshheading:21430287-Lysophospholipids, pubmed-meshheading:21430287-Male, pubmed-meshheading:21430287-Mice, pubmed-meshheading:21430287-Mice, Inbred C57BL, pubmed-meshheading:21430287-Mice, Knockout, pubmed-meshheading:21430287-Microvilli, pubmed-meshheading:21430287-Osmolar Concentration, pubmed-meshheading:21430287-Phosphoproteins, pubmed-meshheading:21430287-Protein Transport, pubmed-meshheading:21430287-Second Messenger Systems, pubmed-meshheading:21430287-Sodium-Hydrogen Antiporter
pubmed:year
2011
pubmed:articleTitle
NHERF2 is necessary for basal activity, second messenger inhibition, and LPA stimulation of NHE3 in mouse distal ileum.
pubmed:affiliation
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural