Fig.7.

Ectopic overexpression of native CHOP, but not the transcriptionally dead leucine zipper domain deficient mutant CHOP (CHOP LZ^–), evokes an increase in BACE1 expression and subsequent Aβ genesis. A) Representative western blots show that the leucine zipper domain of CHOP that is responsible for its transcriptional activity, is necessary to induce BACE1 protein levels as well as the accompanying increase in sAβPPβ and CTFβ levels concomitant with a decrease in sAβPPα and CTFα levels in SH-SY5Y-APP_Swe cells. C, D) Ectopic overexpression of native CHOP (wt CHOP), but not the transcriptionally dead leucine zipper domain deficient mutant CHOP (CHOP LZ^–), elicits an increase in BACE1 mRNA expression (B) and BACE1 activity (C) in SH-SY5Y-APP_Swe cells. D) ELISA immunoassays show that the ectopic overexpression of native CHOP (wt CHOP), but not the transcriptionally dead leucine zipper domain deficient mutant CHOP (CHOP LZ^–), increases the levels of the intracellular Aβ_1 - 42 species in the whole cell lysates and secreted Aβ_1 - 42 species in the conditioned media, from SH-SY5Y-APP_Swe cells. Data is expressed as Mean±S.D and includes determination made in three (n = 3) separate cell culture experiments. ^***p < 0.001 versus empty vector (EV)-transfected cells.