title: Epigenetic control of somatostatin and cortistatin expression by β amyloid peptide.
abstract: β Amyloid, present in senile plaques, has been related largely to neuronal loss in the brain of patients with Alzheimer's disease. However, how neurons respond to β amyloid insults is still poorly understood. Here we show that β amyloid increases somatostatin and cortistatin gene expression mainly through an increase in histone 3 lysine 4 methylation (H3K4me3), a modification associated with transcriptional activation. Somatostatin and cortistatin partially decreased β amyloid toxicity in primary cortical neurons in culture. Thus we suggest that neurons respond to β amyloid insults by releasing somatostatin and cortistatin, which will act as a protective agent against β amyloid toxicity. Our results suggest a relevant function for both neuropeptides against β amyloid toxicity, providing new insights into Alzheimer's disease.
authors.affiliation: Centro de Biología Molecular Severo Ochoa (CSIC-UAM), C/Nicolás Cabrera 1, Universidad Autónoma de Madrid, Campus Cantoblanco, Madrid, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Rubio
authors.forename: José V
authors.initials: JV
authors.lastname: Sánchez-Mut
authors.forename: Esther
authors.initials: E
authors.lastname: García
authors.forename: Zahady D
authors.initials: ZD
authors.lastname: Velasquez
authors.forename: Jorge
authors.initials: J
authors.lastname: Oliver
authors.forename: Manel
authors.initials: M
authors.lastname: Esteller
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004347:Drug Interactions; D004622:Embryo, Mammalian; D057890:Epigenomics; D005786:Gene Expression Regulation / Q000187:drug effects*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D012694:Serine / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D009479:Neuropeptides; D014404:Tubulin; C099323:cortistatin; D012694:Serine; D013004:Somatostatin; D038362:Glycogen Synthase Kinase 3