title: Modulation of amyloid-β protein precursor expression by HspB1.
abstract: Upregulation of heat shock proteins, such as Hsp70 and HspB1/Hsp27, have been associated with an amelioration of the deficits in animal models of Alzheimer's disease (AD). HspB1 is reported to be increased in AD brains and to accumulate in plaques, but whether this localization is an attempt by HspB1 to ameliorate the detrimental effects of amyloid-β (Aβ) on cells or part of the disease process is unknown. Here we explore the potential effects of the HspB1 on amyloid-β protein precursor (AβPP) processing and distribution within HEK293 stable cell lines expressing either AβPPwt or AβPPsw. We compare AβPP production, distribution, and release of proteolytic products (including Aβ40 and Aβ42) to determine possible modifications in the presence of HspB1. We also investigate whether HspB1 interacts with Aβ or its precursor, AβPP, and whether, through this interaction, it is able to alter AβPP processing or release of Aβ peptide. Coexpression of HspB1 resulted in increased cellular holoAβPP as well as C-terminal fragments. Further, expression of HspB1 attenuated the release of Aβ42 from the AβPPsw cells. In summary, we have shown that expression of HspB1 alters AβPP expression and processing in cell lines expressing AβPPwt and AβPPsw. Furthermore, the presence of HspB1 decreased the amount of Aβ42 released by the cell lines. Thus in addition to its effects on protecting cells from the potentially toxic effects of Aβ, HspB1 also appears to be involved in modulating cellular levels of AβPP, although an understanding of the underlying mechanisms requires further investigation.
authors.affiliation: Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: Conway
authors.affiliation: Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Firoozeh
authors.initials: F
authors.lastname: Nafar
authors.affiliation: Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Straka
authors.affiliation: Division of BioMedical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Mearow
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D009154:Mutation / Q000235:genetics; D010446:Peptide Fragments / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins
keywords: AβPPsw; AβPPwt; cell line; protein expression; small heat shock protein