The Systemic Amyloid Precursor Transthyretin (TTR) Behaves as a Neuronal Stress Protein Regulated by HSF1 in SH-SY5Y Human Neuroblastoma Cells and APP23 Alzheimer's Disease Model Mice

• DOI: 10.1523/jneurosci.4936-13.2014
• Publication Date: 2014-05-21T17:05:00Z
• Authors: Xin Wang; Francesca Cattaneo; Lisa Ryno; John Hulleman; Natàlia Reixach; Joel N. Buxbaum
• Keywords: HSF1; Chromatin immunoprecipitation; SH-SY5Y

Increased neuronal synthesis of transthyretin (TTR) may favorably impact on Alzheimer's disease (AD) because TTR has been shown to inhibit Aβ aggregation and detoxify cell-damaging conformers. The mechanism whereby hippocampal cortical neurons from AD patients APP23 model mice produce more is unknown. We now show that expression in SH-SY5Y human neuroblastoma cells, primary the hippocampus mice, significantly enhanced by heat shock factor 1 (HSF1). Chromatin immunoprecipitation (ChIP) assays demonstrated occupation promoter elements HSF1 hippocampi, murine neurons, but not mouse liver, cultured hepatoma (HepG2) or AC16 cardiomyocytes. Treating cells with stimulator celastrol increased transcription parallel HSP40 , HSP70 HSP90 . With both treatments, ChIP showed occupancy HSF1. In vivo signal liver. Transfection a construct into protein production, which could be blocked shHSF1 antisense. effect neuron specific. HepG2 was either suppressive had no confirming differential effects different cell types.