Linked Life Data

11839752

Source:http://linkedlifedata.com/resource/pubmed/id/11839752

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2002-4-22
pubmed:abstractText
There is increasing evidence that the low-density lipoprotein receptor-related protein (LRP) can function as a signaling link in the central nervous system. To investigate the pathophysiological role of LRP in the central nervous system, we examined the effects of activated alpha(2)-macroglobulin (alpha2M*), a ligand of LRP, on intracellular calcium signaling in cultured rat hippocampal neurons. Neuronal effects of alpha2M* (50 nm) were assessed by a comparison of calcium signals produced in control and alpha2M*-pretreated neurons by N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. alpha2M* pretreatment significantly decreased the calcium signals to NMDA, whereas little change was observed for the signals to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid. Native alpha2M, which is not a ligand for LRP, did not affect signals to NMDA. The receptor-associated protein prevented alpha2M*-induced decrease of calcium responses to NMDA, suggesting that alpha2M* exerted its effects through an LRP-mediated pathway. Experiments changing calcium sources demonstrated that alpha2M* pretreatment altered calcium responses to NMDA by primarily changing extracellular calcium influx and subsequently affecting calcium release from intracellular calcium stores. Immunoblot analysis demonstrated that alpha2M* caused a reduction in the levels of the NMDA receptor subunit, NMDAR1. These results suggest that alpha2M* can alter the neuronal response to excitatory neurotransmitters and that alpha2M* pretreatment selectively reduced the calcium responses to NMDA by down-regulating the NMDA receptor.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
26
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
14458-66
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
alpha 2-Macroglobulin exposure reduces calcium responses to N-methyl-D-aspartate via low density lipoprotein receptor-related protein in cultured hippocampal neurons.
pubmed:affiliation
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA. qiu@helix.mgh.harvard.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.