Source:http://linkedlifedata.com/resource/pubmed/id/21178110
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2011-3-1
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pubmed:abstractText |
Many Ca(2+)-regulated intracellular processes are involved in the development of neuroinflammation. However, the changes of Ca(2+) signaling in the brain under inflammatory conditions were hardly studied. ATP-induced Ca(2+) signaling is a central event of signal transmission in astrocytic networks. We investigated primary astrocytes after proinflammatory stimulation with lipopolysaccharide (LPS; 100 ng/ml) for 6-24 h. We reveal that Ca(2+) responses to purinergic ATP stimulation are significantly increased in amplitude and duration after stimulation with LPS. We detected that increased amplitudes of Ca(2+) responses to ATP in LPS-treated astrocytes can be explained by substantial increase of Ca(2+) load in stores in endoplasmic reticulum. The mechanism implies enhanced Ca(2+) store refilling due to the amplification of capacitative Ca(2+) entry. The reason for the increased duration of Ca(2+) responses in LPS-treated cells is also the amplified capacitative Ca(2+) entry. Next, we established that the molecular mechanism for the LPS-induced amplification of Ca(2+) responses in astrocytes is increased expression and activity of VIA phospholipase A(2) (VIA iPLA(2)). Indeed, both gene silencing with specific small interfering RNA and pharmacological inhibition of VIA iPLA(2) with S-bromoenol lactone reduced the load of the Ca(2+) stores and caused a decrease in the amplitudes of Ca(2+) responses in LPS-treated astrocytes to values, which were comparable with those in untreated cells. Our findings highlight a novel regulatory role of VIA iPLA(2) in development of inflammation in brain. We suggest that this enzyme might be a possible target for treatment of pathologies related to brain inflammation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Group VI Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides,
http://linkedlifedata.com/resource/pubmed/chemical/Pla2g6 protein, rat
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1522-1563
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
300
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
C542-9
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pubmed:meshHeading |
pubmed-meshheading:21178110-Animals,
pubmed-meshheading:21178110-Animals, Newborn,
pubmed-meshheading:21178110-Astrocytes,
pubmed-meshheading:21178110-Calcium,
pubmed-meshheading:21178110-Calcium Signaling,
pubmed-meshheading:21178110-Cells, Cultured,
pubmed-meshheading:21178110-Endoplasmic Reticulum,
pubmed-meshheading:21178110-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:21178110-Gene Silencing,
pubmed-meshheading:21178110-Gliosis,
pubmed-meshheading:21178110-Group VI Phospholipases A2,
pubmed-meshheading:21178110-Inflammation Mediators,
pubmed-meshheading:21178110-Lipopolysaccharides,
pubmed-meshheading:21178110-Rats,
pubmed-meshheading:21178110-Up-Regulation
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pubmed:year |
2011
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pubmed:articleTitle |
Proinflammatory treatment of astrocytes with lipopolysaccharide results in augmented Ca2+ signaling through increased expression of via phospholipase A2 (iPLA2).
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pubmed:affiliation |
Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Straße 44, 39120 Magdeburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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