title: Mechanism of protein phosphatase-2Aregulating phosphorylation of amyloid precursor proteosome and Aβ generation.
abstract: OBJECTIVE
  To discuss whether PP-2A influences the phosphorylation level at APP threonine 668 locus thus regulating Aβ secretion.
  
  
  METHODS
  In the experiment, 24 hours after N2a cells of stably transfected human APP (N2a/APP) were treated with okadaic acid (OA) or DES (C6-ceramide) (N2a/APP), an injection of OA cerebral stereotactic was administered to a SD rat in the hippocampal region, or PP-2A overexpressed plasmids was transfected transiently, the aggregate levels of APP phosphorylated APP, and APP-CTF were detected through immunoblotting and the activity of PP-2A and secretase was also detected using a reagent kit.
  
  
  RESULTS
  The phosphorylation level of APP was significantly increased after the PP-2A activity was inhibited by OA. DES activated PP-2A or over-expressed PP-2A was able to reduce the phosphorylation level of APP. Either can inhibit PP and reduce the phosphorylation level of APP. The level of phosphorylated APP was increased significantly after the SD rat was injected with OA through the hippocampal region. The activity of β- and γ-secretases in N2a/APP cells significantly increased after OA treatment whereas the α-secretase activity had no significant changes; the Aβ level increased.
  
  
  CONCLUSIONS
  We discovered that PP-2A was capable of regulating the Aβ level by regulating APP phosphorylation level and β and γ-secretase activity(Fig. 5, Ref. 30).
authors: J W
authors: JW
authors: Zhang
authors: L J
authors: LJ
authors: Jing
authors: G
authors: G
authors: Jian
authors: G C
authors: GC
authors: Dong
mesh_terms: D000544:Alzheimer Disease / Q000139:chemically induced / Q000378:metabolism; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D002518:Ceramides / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019319:Okadaic Acid; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002518:Ceramides; C101954:N-caproylsphingosine; D019319:Okadaic Acid; D054648:Protein Phosphatase 2; D053829:Amyloid Precursor Protein Secretases
keywords: Aβ; PP-2A; alzheimer disease; phosphorylation; protein.