Thyroid hormones reverse the UV-induced repression of APP in neuroblastoma cells.
As a precursor of the neurotoxic amyloid-beta 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.
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Instituto de Investigaciones Biomédicas (C.S.I.C.), Consejo Superior de Investigaciones Científicas, Arturo Duperier, 4, 28029 Madrid, Spain.
Zambrano
Alberto
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López
Eva
E
Pascual
Angel
A
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D009447:Neuroblastoma; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation; D014284:Triiodothyronine / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D016159:Tumor Suppressor Protein p53; D014284:Triiodothyronine