Thyroid hormones reverse the UV-induced repression of APP in neuroblastoma cells

Edited by Jesus Avila

Received 27 March 2009; received in revised form 2 June 2009; accepted 22 June 2009. published online 29 June 2009.

Abstract

As a precursor of the neurotoxic amyloid-β peptide, APP plays a central role in Alzheimer’s disease. We have recently reported that the tumor suppressor p53 inhibits APP gene transcription through the same DNA sequences that mediate an inhibitory effect of thyroid hormones. Now, we have analyzed whether the thyroid hormone T3 can modulate the effects of p53 on APP expression. Exposition to UVC radiation leads to a marked decrease of intracellular APP levels that is paradoxically reversed by T3. Repression by UVC and reversion by the hormone are not observed in cells depleted of p53, demonstrating a p53-dependent mechanism. These results suggest the existence of a cross-talk between p53 and T3 that could play an important role in Alzheimer´s disease.

Keywords: Alzheimer’s disease, Amyloid precursor protein, Neuroblastoma cell, p53, Thyroid hormone, Gene expression

Instituto de Investigaciones Biomédicas (C.S.I.C.), Consejo Superior de Investigaciones Científicas, Arturo Duperier, 4, 28029 Madrid, Spain

Corresponding author. Fax: +34 91 585 4401.

PII: S0014-5793(09)00497-9

doi:10.1016/j.febslet.2009.06.040

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