title: Modulation of neutrophil apoptosis by beta-amyloid proteins.
abstract: This study examined the effect of amyloid beta peptide (Abeta) and the secretase inhibitors of amyloid precursor proteins (APP) on the spontaneous apoptosis of neutrophils. Abeta(1-40) decreased the apoptotic rate of neutrophils. The delayed apoptosis by Abeta was not blocked by pertussis toxin and N-formyl peptide receptor-like 1 antagonistic peptide, WRWWWW. The inhibitors of phoshoinositide 3-kinase (LY294002), phospholipase C (U73122), or Ca++-dependent protein kinase C (Go6976) abrogated the anti-apoptotic effect of Abeta on neutrophils. Moreover, the Abeta-induced delay of apoptosis was inhibited by a calcium chelator, BAPTA/AM. The amount of the APP protein was reduced in the cultured neutrophils and the APP level in the Abeta or pancaspase-treated neutrophils was lower than that in the cultured neutrophils. However, the reduction in APP level was recovered after treating them with the secretase inhibitors or anti-Fas antibody. The exogenous addition of cell permeable beta- and gamma-secretase inhibitors resulted in an increase in the rate of the apoptosis. The regulation of neutrophil apoptosis by the addition of Abeta and secretase inhibitors occurred via the caspase -8, -9, -3, and mitochondrial-dependent pathways. This suggests that the intracellular beta-amyloid proteins play a role as regulating factor of neutrophil survival and that Abeta-induced delay of apoptosis is mediated by other receptors rather than a seven-transmembrane G protein-coupled receptor(s).
authors.affiliation: Department of Biochemistry, College of Medicine, Dong-A University, Busan 602-714, Korea.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Park
authors.forename: Joo-In
authors.initials: JI
authors.lastname: Park
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Baek
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Lee
authors.forename: Jun-O
authors.initials: JO
authors.lastname: Jin
authors.forename: Ja-Woong
authors.initials: JW
authors.lastname: Kim
authors.forename: Young-Seoub
authors.initials: YS
authors.lastname: Hong
authors.forename: Yong-Hwan
authors.initials: YH
authors.lastname: Lee
authors.forename: Jong-Young
authors.initials: JY
authors.lastname: Kwak
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D051017:Apoptosis Regulatory Proteins; D010446:Peptide Fragments; D011480:Protease Inhibitors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human