title: Neuronal cell apoptosis by a receptor-binding domain peptide of ApoE4, not through low-density lipoprotein receptor-related protein.
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.
authors.affiliation: Department of Applied Chemistry, Keio University, Yokohama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Y
authors.initials: Y
authors.lastname: Hashimoto
authors.forename: T
authors.initials: T
authors.lastname: Niikura
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: K
authors.initials: K
authors.lastname: Terashita
authors.forename: Y
authors.initials: Y
authors.lastname: Kita
authors.forename: I
authors.initials: I
authors.lastname: Nishimoto
authors.forename: K
authors.initials: K
authors.lastname: Umezawa
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001665:Binding Sites; D061945:Caspase Inhibitors; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D006801:Humans; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000502:physiology*; D011973:Receptors, LDL / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010446:Peptide Fragments; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D011994:Recombinant Proteins