Apolipoprotein E activates Akt pathway in neuro-2a in an isoform-specific manner.
Apolipoprotein E (apoE) is a ligand for members of the low density lipoprotein (LDL) receptor family, receptors highly expressed in neurons. A study of one of the mechanisms by which apoE might affect neuronal cell metabolism is reported herein. ApoE can induce Akt/protein kinase B phosphorylation in Neuro-2a via two different pathways. Both pathways are mediated by phosphatidylinositol 3-kinase and cAMP-dependent protein kinase. The first pathway is stimulated by apoE3 and E4, but not by E2, after a 1-h incubation. The process requires the binding of apoE to the heparan sulfate proteoglycan/LDL receptor-related protein complex. The second pathway is activated after a 2-h incubation of the cells, in another isoform-dependent manner (E2 = E3 dbl greater-than sign E4) and is mediated by calcium. Our results suggest that apoE might affect cell metabolism and survival in neurons in an isoform-specific manner by inducing novel signaling pathways.
Laffont
Isabelle
I
Department of Biochemistry, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Takahashi
Motoko
M
Shibukawa
Yukinao
Y
Honke
Koichi
K
Shuvaev
Vladimir V
VV
Siest
Gérard
G
Visvikis
Sophie
S
Taniguchi
Naoyuki
N
D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D007700:Kinetics; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D020033:Protein Isoforms / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured
D001057:Apolipoproteins E; D002118:Calcium; D017868:Cyclic AMP-Dependent Protein Kinases; D026502:LDL-Receptor Related Proteins; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases; D010768:Phosphoserine; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt