|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2003-11-19
|
|
pubmed:abstractText |
Glycogen synthase kinase-3beta (GSK-3beta) is implicated in regulating apoptosis and tau protein hyperphosphorylation in Alzheimer's disease (AD). We investigated the effects of two key AD molecules, namely apoE (E3 and E4 isoforms) and beta-amyloid (Abeta) 1-42 on GSK-3beta and its major upstream regulators, intracellular calcium and protein kinases C and B (PKC and PKB) in human SH-SY5Y neuroblastoma cells. ApoE3 induced a mild, transient, Ca2+-independent and early activation of GSK-3beta. ApoE4 effects were biphasic, with an early strong GSK-3beta activation that was partially dependent on extracellular Ca2+, followed by a GSK-3beta inactivation. ApoE4 also activated PKC-alpha and PKB possibly giving the subsequent GSK-3beta inhibition. Abeta(1-42) effects were also biphasic with a strong activation dependent partially on extracellular Ca2+ followed by an inactivation. Abeta(1-42) induced an early and potent activation of PKC-alpha and a late decrease of PKB activity. ApoE4 and Abeta(1-42) were more toxic than apoE3 as shown by MTT reduction assays and generation of activated caspase-3. ApoE4 and Abeta(1-42)-induced early activation of GSK-3beta could lead to apoptosis and tau hyperphosphorylation. A late inhibition of GSK-3beta through activation of upstream kinases likely compensates the effects of apoE4 and Abeta(1-42) on GSK-3beta, the unbalanced regulation of which may contribute to AD pathology.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein E3,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoprotein E4,
http://linkedlifedata.com/resource/pubmed/chemical/Apolipoproteins E,
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Serum-Free,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/PRKCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/amyloid beta-protein (1-42),
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0022-3042
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
87
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1152-64
|
|
pubmed:dateRevised |
2011-11-2
|
|
pubmed:meshHeading |
pubmed-meshheading:14622095-Amyloid beta-Peptides,
pubmed-meshheading:14622095-Apolipoprotein E3,
pubmed-meshheading:14622095-Apolipoprotein E4,
pubmed-meshheading:14622095-Apolipoproteins E,
pubmed-meshheading:14622095-Calcium,
pubmed-meshheading:14622095-Caspase 3,
pubmed-meshheading:14622095-Caspases,
pubmed-meshheading:14622095-Cell Line, Tumor,
pubmed-meshheading:14622095-Cell Survival,
pubmed-meshheading:14622095-Culture Media, Serum-Free,
pubmed-meshheading:14622095-Cytoskeletal Proteins,
pubmed-meshheading:14622095-Enzyme Activation,
pubmed-meshheading:14622095-Glycogen Synthase Kinase 3,
pubmed-meshheading:14622095-Humans,
pubmed-meshheading:14622095-Neuroblastoma,
pubmed-meshheading:14622095-Peptide Fragments,
pubmed-meshheading:14622095-Phosphorylation,
pubmed-meshheading:14622095-Protein Isoforms,
pubmed-meshheading:14622095-Protein Kinase C,
pubmed-meshheading:14622095-Protein Kinase C-alpha,
pubmed-meshheading:14622095-Protein Transport,
pubmed-meshheading:14622095-Protein-Serine-Threonine Kinases,
pubmed-meshheading:14622095-Proto-Oncogene Proteins,
pubmed-meshheading:14622095-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:14622095-Trans-Activators,
pubmed-meshheading:14622095-beta Catenin
|
|
pubmed:year |
2003
|
|
pubmed:articleTitle |
Apolipoprotein E and beta-amyloid (1-42) regulation of glycogen synthase kinase-3beta.
|
|
pubmed:affiliation |
Neurotec, Section for Experimental Geriatrics, Karolinska Institutet, NOVUM, KFC, plan 4, S-141 86 Huddinge, Sweden. Angel.Cedazo-Mínguez@neurotec.ki.se
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
