title: Apolipoprotein E and mimetic peptide initiate a calcium-dependent signaling response in macrophages.
abstract: Apolipoprotein E (ApoE) is a 34-kDa cholesterol transport protein that also possesses immunomodulatory properties. In this study, we demonstrate that ApoE initiates a signaling cascade in murine peritoneal macrophages that leads to increased production of inositol triphosphate with mobilization of intracellular Ca(2+) stores. This cascade is inhibited by pretreatment with receptor-associated protein and Ni(2+), and it is mediated by a pertussis toxin-sensitive G protein. These properties are characteristic of signal transduction induced via ligand binding to the cellular receptor, lipoprotein receptor-related protein. A peptide derived from the receptor-binding region of ApoE also initiates signal transduction in a manner similar to that of the intact protein, suggesting that this isolated region is sufficient for signal transduction. The ApoE-mimetic peptide competed for binding with the intact protein, confirming that they both interact with the same site. ApoE-dependent signal transduction might play a role in mediating the functional properties of this lipoprotein.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: U K
authors.initials: UK
authors.lastname: Misra
authors.forename: C L
authors.initials: CL
authors.lastname: Adlakha
authors.forename: G
authors.initials: G
authors.lastname: Gawdi
authors.forename: M K
authors.initials: MK
authors.lastname: McMillian
authors.forename: S V
authors.initials: SV
authors.lastname: Pizzo
authors.forename: D T
authors.initials: DT
authors.lastname: Laskowitz
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology*; D001667:Binding, Competitive; D020013:Calcium Signaling; D002478:Cells, Cultured; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007700:Kinetics; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009532:Nickel / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D037342:Pertussis Toxin; D011971:Receptors, Immunologic / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D001057:Apolipoproteins E; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D010455:Peptides; D011971:Receptors, Immunologic; D010566:Virulence Factors, Bordetella; D009532:Nickel; D015544:Inositol 1,4,5-Trisphosphate; D037342:Pertussis Toxin