Linked Life Data

15169786

Source:http://linkedlifedata.com/resource/pubmed/id/15169786

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2004-8-9
pubmed:abstractText
Several ligands of the endocytic low density lipoprotein receptor-related protein (LRP), such as apoE-containing lipoproteins and activated alpha2-macroglobulin (alpha2M*), promote neurite outgrowth, suggesting that LRP may have signaling functions. In this study, we found that the treatment of neurons with alpha2M* significantly increased the individual length (by 71%) and numbers (by 139%) of neurites of primary mouse cortical neurons. These effects were blocked by the LRP antagonist, the receptor-associated protein. We found similar neurite outgrowth with purified apoE3 and a tandem apoE peptide containing only the receptor-binding domain. To investigate the intracellular pathway of the LRP signaling involved in neurite outgrowth, we tested the effects of alpha2M* on the phosphorylation of the mitogen-activated protein (MAP) extracellular signal-regulated kinases 1 and 2 (ERK1/2). We found that 1) phospho-MAP kinase levels were altered within 30 min after treatment with alpha2M*, 2) the MAP kinase inhibitor, PD98059, specifically blocked the alpha2M*-induced neurite outgrowth, 3) manipulating intracellular calcium by BayK or BAPTA altered the neurite outgrowth and associated changes in the phospho-MAP kinase levels, which were blunted by alpha2M*, 4) alpha2M* promoted the phosphorylation of the transcription factor CREB through MAP kinase, and 5) LRP-specific antibodies increased levels of phosphorylated MAP kinase and phosphorylated CREB. The effects of alpha2M*, apoE3, and apoE peptides increased LRP levels in the cortical neurons, whereas LRP receptor-associated protein reduced dendritic LRP expression. These results demonstrate that p44/42 MAP kinase plays an important role in LRP-mediated neurite outgrowth with activation involving the effects on calcium homeostasis and downstream effects involving the activation of gene transcription through CREB.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34948-56
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15169786-Animals, pubmed-meshheading:15169786-Blotting, Western, pubmed-meshheading:15169786-Calcium, pubmed-meshheading:15169786-Enzyme Inhibitors, pubmed-meshheading:15169786-Flavonoids, pubmed-meshheading:15169786-Ligands, pubmed-meshheading:15169786-Low Density Lipoprotein Receptor-Related Protein-1, pubmed-meshheading:15169786-MAP Kinase Signaling System, pubmed-meshheading:15169786-Mice, pubmed-meshheading:15169786-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:15169786-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:15169786-Mitogen-Activated Protein Kinases, pubmed-meshheading:15169786-Models, Biological, pubmed-meshheading:15169786-Neurons, pubmed-meshheading:15169786-Phosphorylation, pubmed-meshheading:15169786-Signal Transduction, pubmed-meshheading:15169786-Time Factors
pubmed:year
2004
pubmed:articleTitle
Apolipoprotein E receptors mediate neurite outgrowth through activation of p44/42 mitogen-activated protein kinase in primary neurons.
pubmed:affiliation
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.