Linked Life Data

17664275

Source:http://linkedlifedata.com/resource/pubmed/id/17664275

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
2007-9-14
pubmed:abstractText
The function and regulation of Na(+)/H(+) exchanger isoform 1 (NHE1) following cerebral ischemia are not well understood. In this study, we demonstrate that extracellular signal-related kinases (ERK1/2) play a role in stimulation of neuronal NHE1 following in vitro ischemia. NHE1 activity was significantly increased during 10-60 min reoxygenation (REOX) after 2-h oxygen and glucose deprivation (OGD). OGD/REOX not only increased the V(max) for NHE1 but also shifted the K(m) toward decreased [H(+)](i). These changes in NHE1 kinetics were absent when MAPK/ERK kinase (MEK) was inhibited by the MEK inhibitor U0126. There were no changes in the levels of phosphorylated ERK1/2 (p-ERK1/2) after 2 h OGD. The p-ERK1/2 level was significantly increased during 10-60 min REOX, which was accompanied by nuclear translocation. U0126 abolished REOX-induced elevation and translocation of p-ERK1/2. We further examined the ERK/90-kDa ribosomal S6 kinase (p90(RSK)) signaling pathways. At 10 min REOX, phosphorylated NHE1 was increased with a concurrent elevation of phosphorylation of p90(RSK), a known NHE1 kinase. Inhibition of MEK activity with U0126 abolished phosphorylation of both NHE1 and p90(RSK). Moreover, neuroprotection was observed with U0126 or genetic ablation or pharmacological inhibition of NHE1 following OGD/REOX. Taken together, these results suggest that activation of ERK1/2-p90(RSK) pathways following in vitro ischemia phosphorylates NHE1 and increases its activity, which subsequently contributes to neuronal damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28274-84
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17664275-Active Transport, Cell Nucleus, pubmed-meshheading:17664275-Animals, pubmed-meshheading:17664275-Cation Transport Proteins, pubmed-meshheading:17664275-Hydrogen-Ion Concentration, pubmed-meshheading:17664275-Ischemia, pubmed-meshheading:17664275-Kinetics, pubmed-meshheading:17664275-Membrane Proteins, pubmed-meshheading:17664275-Mice, pubmed-meshheading:17664275-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:17664275-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:17664275-Neurons, pubmed-meshheading:17664275-Phosphoproteins, pubmed-meshheading:17664275-Phosphorylation, pubmed-meshheading:17664275-Ribosomal Protein S6 Kinases, 90-kDa, pubmed-meshheading:17664275-Signal Transduction, pubmed-meshheading:17664275-Sodium-Hydrogen Antiporter, pubmed-meshheading:17664275-Time Factors
pubmed:year
2007
pubmed:articleTitle
ERK1/2-p90RSK-mediated phosphorylation of Na+/H+ exchanger isoform 1. A role in ischemic neuronal death.
pubmed:affiliation
Department of Physiology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural