Linked Life Data

19717566

Source:http://linkedlifedata.com/resource/pubmed/id/19717566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Apolipoprotein E-containing lipoproteins (LpE) are generated in the central nervous system by glial cells, primarily astrocytes, and are recognized as key players in lipid metabolism and transport in the brain. We previously reported that LpE protect retinal ganglion neurons from apoptosis induced by withdrawal of trophic additives (Hayashi, H., Campenot, R. B., Vance, D. E., and Vance, J. E. (2007) J. Neurosci. 27, 1933-1941). LpE bind to low density lipoprotein receptor-related protein-1 and initiate a signaling pathway that involves activation of protein kinase Cdelta and inhibition of the pro-apoptotic glycogen synthase kinase-3beta. We now show that uptake of LpE is not required for the neuroprotection. Experiments with inhibitors of phospholipase Cgamma1 and RNAi knockdown studies demonstrate that activation of phospholipase Cgamma1 is required for the anti-apoptotic signaling pathway induced by LpE. In addition, the protein phosphatase-2B, calcineurin, is involved in a neuronal death pathway induced by removal of trophic additives, and LpE inhibit calcineurin activation. LpE also attenuate neuronal death caused by oxidative stress. Moreover, physiologically relevant apoE3-containing lipoproteins generated by apoE3 knock-in mouse astrocytes more effectively protect neurons from apoptosis than do apoE4-containing lipoproteins. Because inheritance of the apoE4 allele is the strongest known genetic risk factor for Alzheimer disease, the reduced neuroprotection afforded by apoE4-containing LpE might contribute to the neurodegeneration characteristic of this disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
284
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
29605-13
pubmed:dateRevised
2010-10-26
pubmed:meshHeading
pubmed-meshheading:19717566-Alleles, pubmed-meshheading:19717566-Alzheimer Disease, pubmed-meshheading:19717566-Animals, pubmed-meshheading:19717566-Apolipoprotein E3, pubmed-meshheading:19717566-Apolipoprotein E4, pubmed-meshheading:19717566-Apoptosis, pubmed-meshheading:19717566-Astrocytes, pubmed-meshheading:19717566-Calcineurin, pubmed-meshheading:19717566-Enzyme Activation, pubmed-meshheading:19717566-Glycogen Synthase Kinase 3, pubmed-meshheading:19717566-Humans, pubmed-meshheading:19717566-Mice, pubmed-meshheading:19717566-Mice, Knockout, pubmed-meshheading:19717566-Neurons, pubmed-meshheading:19717566-Phospholipase C gamma, pubmed-meshheading:19717566-Rats, pubmed-meshheading:19717566-Rats, Sprague-Dawley, pubmed-meshheading:19717566-Receptors, LDL, pubmed-meshheading:19717566-Risk Factors, pubmed-meshheading:19717566-Signal Transduction, pubmed-meshheading:19717566-Tumor Suppressor Proteins
pubmed:year
2009
pubmed:articleTitle
Protection of neurons from apoptosis by apolipoprotein E-containing lipoproteins does not require lipoprotein uptake and involves activation of phospholipase Cgamma1 and inhibition of calcineurin.
pubmed:affiliation
Priority Organization for Innovation and Excellence, Kumamoto University, Kumamoto 860-8556, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't