NDLI: Apolipoprotein E Receptors Mediate the Effects of β-Amyloid on Astrocyte Cultures

Content Provider	Journal of Biological Chemistry (JBC)
Author	LaDu, Mary Jo Shah, Javeed Ali Reardon, Catherine A. Getz, Godfrey S. Bu, Guojun Hu, Jingru Guo, Ling Eldik, Linda J. Van
Abstract	We have previously shown that β-amyloid (Aβ) induces astrocyte activation in vitro and that this reaction is attenuated by the addition of exogenous apolipoprotein E (apoE)-containing particles. However, the effects of Aβ on endogenous apoE and apoJ levels and the potential role of apoE receptors in astrocyte activation have not been addressed. Three activating stimuli (lipopolysaccharide, dibutyryl cAMP, and aged Aβ 1–42) were used to induce activation of rat astrocyte cultures, as assessed by changes in morphology and an increase in interleukin-1β. However, only Aβ also induced ∼50% reduction in the amount of released apoE and apoJ and an 8-fold increase in the levels of cell-associated apoE and apoJ. Experiments using two concentrations of receptor-associated protein, an inhibitor of apoE receptors with a differential affinity for the low density lipoprotein receptor (LDLR) and the LDLR-related protein (LRP), suggest that LRP mediates Aβ-induced astrocyte activation, whereas LDLR mediates the Aβ-induced changes in apoE levels. Receptor-associated protein had no effect on apoJ levels or on activation by either dibutyryl cAMP or lipopolysaccharide. These data suggest that apoE receptors translate the presence of extracellular Aβ into cellular responses, both initiating and modulating the inflammatory response induced by Aβ.
Related Links	http://www.jbc.org/content/275/43/33974.abstract
Ending Page	33980
Starting Page	33974
Page Count	7
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	43
Volume Number	275
DOI	10.1074/jbc.M000602200
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2000-10-27
Access Restriction	Open
Subject Keyword	Alzheimer's disease (AD) Β-amyloid (Aβ) Low density lipoprotein receptor (LDLR) LDLR-related protein (LRP) Apolipoprotein E and J (apoE and apoJ) Interleukin (IL) Receptor-associated protein (RAP) Phosphate-buffered saline (PBS) Lipopolysaccharide (LPS) Dibutyryl cyclic AMP (dbcAMP) Glial fibrillary acidic protein (GFAP) MECHANISMS OF SIGNAL TRANSDUCTION
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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