Neuronal cell apoptosis by a receptor-binding domain peptide of ApoE4, not through low-density lipoprotein receptor-related protein

Biochem Biophys Res Commun. 2000 Nov 30;278(3):633-9. doi: 10.1006/bbrc.2000.3841.

Abstract

Since an apolipoprotein E4 (ApoE4) peptide composed of the low-density lipoprotein (LDL) receptor-related protein (LRP)-binding domain [ApoE4(141-149)(2) or ApoE(141-155)(2)] exerts neurotoxicity in primary neurons and neuronal cell lines, it has been controversial whether these effects are mediated by LRP. Here, we examined whether ApoE4(141-149)(2)-induced toxicity is mediated by LRP in a neuronal cell system where ApoE4 toxicity is mediated by LRP: serum-deprived F11 neuronal cells. In these cells, where ApoE4 exerted toxicity by apoptosis in a manner sensitive to both caspase inhibitors and pertussis toxin (PTX), ApoE4(141-149)(2) also caused cell death by apoptosis but in a caspase-inhibitor-resistant, PTX-resistant manner. ApoE4(141-149)(2)-induced death was not inhibited by antisense oligonucleotides to LRP. Therefore, we conclude that ApoE4(141-149)(2) is able to exert neurotoxicity without involving LRP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apolipoprotein E4
  • Apolipoproteins E / chemistry
  • Apolipoproteins E / pharmacology
  • Apolipoproteins E / physiology*
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Binding Sites
  • Caspase Inhibitors
  • Cell Line
  • Cell Survival / drug effects
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Mice
  • Molecular Sequence Data
  • Neurons / cytology*
  • Neurons / physiology*
  • Peptide Fragments / pharmacology*
  • Receptors, Immunologic / physiology*
  • Receptors, LDL / physiology*
  • Recombinant Proteins / metabolism
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Peptide Fragments
  • Receptors, Immunologic
  • Receptors, LDL
  • Recombinant Proteins