Apolipoprotein E receptors mediate the effects of β-amyloid on astrocyte cultures

Mary Jo Ladu, Javeed Ali Shah, Catherine A. Reardon, Godfrey S. Getz, Guojun Bu, Jingru Hu, Ling Guo, Linda J. Van Eldik

Research output: Contribution to journalArticle

77 Scopus citations

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 lipoproiein 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.

Original languageEnglish (US)
Pages (from-to)33974-33980
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number43
DOIs
StatePublished - Oct 27 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Ladu, M. J., Shah, J. A., Reardon, C. A., Getz, G. S., Bu, G., Hu, J., Guo, L., & Van Eldik, L. J. (2000). Apolipoprotein E receptors mediate the effects of β-amyloid on astrocyte cultures. Journal of Biological Chemistry, 275(43), 33974-33980. https://doi.org/10.1074/jbc.M000602200