PMID: 9540849Apr 16, 1998Paper

Amyloid precursor protein heat shock response in lymphoblastoid cell lines bearing presenilin-1 mutations

Biochimica Et Biophysica Acta
J A JohnstonR F Cowburn

Abstract

The amyloid precursor protein (APP) gene promoter contains a heat shock element. An abnormal APP heat shock response could increase accumulation of A beta, the APP metabolite found in Alzheimer's disease amyloid plaques. Since A beta production is affected by presenilin-1 (PS-1) mutations, we investigated whether basal APP levels or response to heat shock were altered in lymphoblastoid cell lines from 8 PS-1 mutation-bearers and 9 control members of Alzheimer's disease families. Lymphoblastoid cell lines were incubated at 42 degrees C for 35 min and allowed to recover at 37 degrees C for 1, 3, 8, 24 and 48 h. APP mRNA levels, quantified using RNA-RNA solution hybridisation, increased significantly at 1 and 3 h post-heat shock to between 123% and 163% of pre-heat shock (0 h) levels and returned to normal by 8 h. Semi-quantitative Western immunoblotting of cell lysates using the 22C11 antibody detected two major bands, migrating at approximately 145 and approximately 120 kDa. Band optical densities increased significantly at 3 h to approximately 155% of 0 h levels, following the increase in APP mRNA levels and showing a similar reversibility. APP mRNA and protein responses were comparable in the PS-1 mutation-bearing and control ...Continue Reading

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Citations

Mar 9, 2018·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Tsuneya IkezuLindsay A Farrer

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